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Purpose: To investigate radial peripapillary capillary (RPC) network in patients affected by retinitis pigmentosa (RP)., Methods: Eleven patients (22 eyes) with previous diagnosis of RP and 16 age-matched healthy subjects (16 eyes) were enrolled. The diagnosis of RP was made based on both clinical features and electrophysiological examination. All patients underwent a complete ophthalmologic examination, including optical coherence tomography angiography and visual field (VF). The primary outcomes were the RPC vessel density in the peripapillary and disk areas; the secondary outcomes were the peripapillary retinal nerve fiber layer (RNFL) thickness and the mean defect at VF., Results: A total of 19 eyes of 11 RP patients (5 males, 6 females) and 16 eyes of 16 healthy subjects (10 males, 6 females) were included for the analysis. RPC vessel density in the disk area was 46.5 ± 7.1% in the RP group and 45.4 ± 10.6% in the control group ( p  = 0.754). RPC vessel density in the peripapillary area was significantly reduced in the RP group after the comparison with the control group (52.5 ± 5.0 and 57.2 ± 5.1%, respectively, p  = 0.011). RNFL thickness was 85.9 ± 20.4 μm in the RP group and 104.0 ± 6.4 μm in the control group ( p  = 0.002). RPC vessel density was significantly correlated with RNFL thickness values in RP patients, both in the disk and in the peripapillary area (Rho = 0.599 and p  = 0.007 in the disk area, Rho = 0.665 and p  = 0.002 in the peripapillary area, respectively)., Conclusion: We showed that density of RPC is reduced in these patients in the peripapillary area. Moreover, the RPC vessel density correlates with the RNFL thickness.

Aim: To investigate foveal avascular zone (FAZ) and parafoveal vessel densities (PRVD) by means of optical coherence tomography angiography (OCTA) in diabetic patients with or without diabetic retinopathy (DR) and to assess the reproducibility of FAZ and PRVD measurements., Methods: Sixty diabetic patients (60 eyes) with different stage of DR (graded according to the International Clinical Severity Scale for DR) and 20 healthy subjects underwent FAZ area and PRVD measurements using OCTA by two experienced examiners. FAZ area in all patients was also assessed using fluorescein angiography (FA)., Results: In subject with proliferative DR and with moderate-severe non proliferative DR, FAZ area was significantly increased compared to healthy controls ( P =0.025 and P =0.050 respectively measured with OCTA and P =0.025 and P =0.048 respectively measured with FA). OCTA showed significantly less inter-observer variability compared to FA. Concordance correlation coefficient (CCC) for FAZ area measurements was 0.829 (95%CI: 0.736-0.891) P <0.001 with FA and 1.000 (95%CI: 0.999-1.000) P <0.001 with OCTA. CCC was 0.834 (95%CI: 0.746-0.893) P <0.001 and 0.890 (95%CI: 0.828-0.930) P <0.001 for parafoveal superficial and deep vessel density measurements, respectively., Conclusion: OCTA shows progressive increase of FAZ area and reduction of PRVD in both superficial and deep plexus at increasing DR severity. FAZ area and PRVD measurements using OCTA are highly reproducible.

Ocular surface diseases (OSDs) represent a widely investigated field of research given their growing incidence and the negative impact on quality of life. During OSDs, cytokines generated by damaged epithelia trigger and deregulate the lymphoid cells composing the eye-associated lymphoid tissues, inducing an immune-mediated chronic inflammation that amplifies and propagates the disease during time. The conjunctiva-associated lymphoid tissue (CALT), given its particular position that permits immune cells covering the cornea, might play a crucial role in the development of OSDs. Despite the recognized inflammatory role of mucosa-associated lymphoid tissues in other stations taking contact with the external environment (gut or bronchus), CALT did not gain the deserved consideration. In the last years, the diffusion of the in vivo confocal microscopy (IVCM) stimulated the interest to CALT, especially in dry eye, ocular allergy, and glaucoma. Though the initial stimuli were different, IVCM documented similar changes, represented by increased lymphoid cells within the diffuse layer, follicles and interfollicular spaces. These findings, which need to be validated by immunohistology, support the CALT stimulation during OSDs. However, while an involvement of the CALT in OSDs is hypothesizable, the exact role of this structure in their pathogenesis remains unclear and warrants further investigations.

A rotating polarimetric 90°-cross linear-filter interferometry system was used to detect the morphological characteristics and features of interference patterns produced in in-vivo corneal stroma in healthy human corneas of 23 subjects. The characteristic corneal isogyres presenting with an evident cross-shaped pattern, grossly aligned with the fixation axis, were observed in all patients with centers within the pupillary dark area, impeding the exact determination of the center point. During the rotational scan in 78.3% of the eyes the cross-shaped pattern of the isogyre gradually separated to form two distinct hyperbolic arcs in opposite quadrants, reaching their maximal separation at 45 degrees with respect to angle of cross-shaped pattern formation. The corneal cross and hyperbolic-pattern repeated every 90° throughout the 360° rotational scan. While the interpretation of the isogyres presents particular difficulties, two summary parameters can be extracted for each cornea: the presence/orientation of a single or two dark areas in post-processed images and isochromes. However, the development of dedicated software for semi-quantitative analysis of these parameters and enantiomorphism may become available in the near future. The possible application of polarimetric interferometry in the field of both corneal pathologies and corneal surgery may be of great interest for clinical purposes.

Aims: To investigate associations between changes in retinal vessels and alterations detected by spectral domain optical coherence tomography (SD-OCT) scans in intermediate stage age-related macular degeneration (AMD)., Methods: Thirty eyes of 30 patients with intermediate dry AMD were enrolled in the study. Of the cohort study, 15 eyes (changes-AMD group) showed OCT changes preceding the development of drusen-associated atrophy. A control group of healthy subjects was selected for statistical comparisons. All patients underwent an ophthalmologic evaluation, including OCT angiography (OCTA) and SD-OCT scans. Main outcome measures were superficial vessel density, deep vessel density, macular thickness., Results: Foveal macular thickness was 215.2±32.9 μm in changes-AMD patients and was significantly thinner than no changes-AMD patients (248.3±23.3 μm, p=0.002) and healthy subjects (268.1±19.2 μm, p<0.0001). Furthermore, in the parafoveal area, the thicknesses of both the inner retina and the outer retina were reduced in the changes-AMD group, after comparison with the two other groups. Parafoveal superficial vascular plexus flow density was 43.3±2.7% in changes-AMD patients and was decreased compared with the no changes-AMD group (48.7±3.3%, p=0.003) and healthy controls (50.4±6.1%, p=0.001). A direct correlation of the superficial plexus flow density with the inner retina parafoveal macular thickness (R 2 =0.761, p=0.028) was found., Conclusions: We demonstrated an association between SD-OCT signs and retinal blood supply in patients with intermediate AMD and we showed that patients with signs predicting development of geographic atrophy have a reduced flow in superficial vascular plexus and damage of the inner and the outer retina., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.)

The purpose of this study was to evaluate the incidence of opaque bubble layer (OBL) in femtosecond laser-assisted in situ keratomileusis (LASIK) flaps created with the support of Visumax Carl Zeiss femtosecond laser, planned with different flap diameters (7.90, 8.0, and 8.20 mm) and the same laser energy and power settings. Incidence of intraoperative OBL in flaps of consecutive 108 patients (216 eyes) subjected to bilateral femtosecond-assisted LASIK was considered. Flap creation was performed with the same laser design parameters (spot distance and energy offset) and different presetting diameters of 7.90 mm (72 eyes, group 1), 8 mm (72 eyes, group 2), and 8.20 mm (72 eyes, group 3). The incidence of OBL was considered and its extension was reported measuring involvement of different four corneal flap quadrants in which was theoretically divided the entire flap area; based on these data, OBL presence was classified as none (no evidence of OBL), minimal (minimal presence in not more that one quadrants corneal flap), mild (OBL presence in almost two or three quadrants without tendency to invade central cornea), and moderate (OBL presence in almost three quadrants with tendency to invade central cornea). In group 1, the incidence of OBL was of 23.6 % (17 eyes) with a mild/moderate presence; in group 2, incidence was 20.8 % (15 eyes) with mild presence. Group 3 presented a reduced OBL incidence (4.1 %, 3 eye) with a minimal presence. No statistically significant difference was found between group 1 and 2 (p = 0.8414).We found statistically significant differences between group 1 and group 3 (p = 0.0012) and between groups 2 and 3 (p = 0.0044). A significant reduction and extension of OBL incidence were evident when LASIK flap settings diameter was increased, and flap edge was closer to the contact glass border; this is probably consequent to a more effective gas dispersion outside of corneal flap.

The authors present the case of a 59-year-old woman in treatment with interferon alfa-2b for stage IV melanoma and widespread metastases who presented with interferon-associated retinopathy. An ocular examination revealed multiple retinal cotton-wool spots and hard exudates. Interferon treatment was suspended. The patient was followed up for 5 months following the baseline visit by means of en face optical coherence tomography (OCT), spectral-domain OCT, and OCT angiography. Multimodal imaging was useful in the follow-up of this condition, permitting the characterization of all the lesions hallmarking the interferon-retinopathy and showing that this illness was related to a reduction of the retinal vascular perfusion. [Ophthalmic Surg Lasers Imaging Retina. 2017;48:498-504.]., (Copyright 2017, SLACK Incorporated.)

Purpose: To assess the reproducibility and repeatability of foveal avascular zone (FAZ) area measurements using swept-source optical coherence tomography angiography (SS-OCTA) in healthy subjects., Methods: Sixty-four eyes of 64 healthy volunteers were randomly subjected to FAZ area measurements using SS-OCTA by 2 examiners in 2 different sessions., Results: The FAZ areas measured by the first and second observer were 0.269 ± 0.092 mm2 and 0.270 ± 0.090 mm2, respectively. Within subjects, the coefficients of variations were 2.44% (95% confidence interval [CI] 1.95% to 2.93%) and 2.66% (95% CI 2.00% to 3.31%) for the first and second observers, respectively. The coefficient of repeatability average measurements of FAZ area were 0.021 mm2 and 0.024 mm2. The intraclass correlation coefficient values were 0.993 (95% CI 0.989 to 0.996) and 0.991 (95% CI 0.986 to 0.995). Interobserver and intraobserver concordance correlation coefficients ranged from 0.998 (95% CI 0.997 to 0.999) to 0.999 (95% CI 0.998 to 0.999) and from 0.989 (95% CI 0.982 to 0.993) to 0.987 (95% CI 0.979 to 0.992), respectively., Conclusions: The FAZ area measurements by means of SS-OCTA showed high reproducibility and repeatability in healthy eyes.

Purpose: To detect corneal inflammation and apoptosis induced after small incision lenticule extraction (SMILE) at different refractive corrections for moderate to high values of myopia., Methods: Fifty patients (50 eyes) suffering from medium to high myopia (spherical equivalent refraction from -3.75 to -10.00 diopters (D) with refractive astigmatism under -0.75 D) underwent SMILE in order to correct myopic error. In vivo evaluation was done by corneal confocal microscopy (IVCM) and ex vivo by immunohistochemistry. After surgery, all corneal lenticules were checked for regularity, entirety, and fixed in formalin for immunohistochemistry evaluation of apoptosis (TUNEL) and inflammation (CD11b) levels. Postoperative assessments took place during the first week and the first and third months after surgery. Patients returned for IVCM examination for analysis of the corneal stromal femtosecond laser treatment interfaces reflectivity., Results: No correlation was observed between treated myopic refractive error and number of CD11b + and TUNEL + cell in all analyzed extracted lenticules. IVCM at 1 week and 1 month of follow-up showed numerous reflective particles at the laser treatment interface with a moderate light scattering. In semi-quantitative analysis of reflectivity intensity at the laser interfaces, a statistical difference was evident only between 1 week and 1 month (p = 0.0213)., Conclusions: SMILE, as an innovative all-femto surgical procedure, results in a reduced tissue inflammation and apoptosis levels with a minimum tissue response, in terms of interface reflectivity, and there are no statistically significant differences among variable treated refractive error range.

Purpose: To assess the epi- and intra-retinal morphology changes of the tangential tractions following vitreoretinal surgery for epiretinal membranes and to investigate the correlation between the depth of retinal changes and functional macular sensitivity (MS)., Methods: This is a prospective cross-sectional interventional study, in which 73 eyes of 73 patients with diagnosis of idiopathic epiretinal membrane (iERM) were evaluated. All patients received complete ophthalmic evaluation, including axial and en-face scanning spectral domain-optical coherence tomography (SD-OCT) analysis and microperimetry. Follow-up examinations were performed preoperatively 1, 3, and 6 months post-vitrectomy for iERM and inner limiting membrane (ILM) peeling. Patients were retrospectively categorized into three groups according to the degree of visual improvement at 6 months postoperatively ("better," "stable," "worse"). The main outcome measures were the changes of depth of traction, which is defined as the first layer without visible retinal folds measured with en-face analysis setting the offset on ILM; ganglion cell complex (GCC) thickness; best-corrected visual acuity (BCVA), and MS., Results: The mean reduction of the depth of the first retinal layer free from traction was 70.10 μm (SD 17.78) in the "better" group (p < 0.001) and 66.56 μm (SD 18.90) in the "stable" group (p < 0.001). A correlation was found between the preoperative depth of the first retinal layer free from traction and postoperative MS improvement (R = 0.47; p = 0.034) only in the "better" group. There was no significant difference in the reduction of traction between the "better" and "stable" groups., Conclusion: The study shows a significant correlation between en-face SD-OCT analysis MS. We found that patients that can significantly benefit from the vitrectomy and iERM-ILM peeling are those with preoperative deeper retinal changes and better BCVA and those without intraretinal cysts. In the presence of superficial retinal changes, the patients do not get any significant functional improvement. The main outcome was visual acuity gain. It is not tested whether patients improved in terms of reduction in metamorfopsia or reduction in binocular complaints.

Purpose: To examine the preoperative conjunctival dendritic cell density (DCD), goblet cell density (GCD), and stromal meshwork reflectivity (SMR) in glaucomatous patients undergoing filtration surgery, using in vivo confocal microscopy (IVCM)., Methods: Sixty-six patients were enrolled. At baseline, IVCM was performed at the site planned for surgery, and was repeated after 12 months at bleb site. Surgery was successful when a one-third reduction of baseline IOP was obtained at the last follow-up. The main outcomes were baseline DCD, GCD, and SMR, and 12 months IOP. The relations between baseline confocal parameters and 12 months IOP were analyzed., Results: Filtration surgery was successful in 43 patients (group 1: complete success, 25; group 2: qualified success, 18), and unsuccessful in 23 patients (group 3). Baseline IOP (mm Hg) was 27.6 ± 2.8, 28.8 ± 4.1, and 27.7 ± 3.2 in groups 1 to 3, respectively. Preoperative DCD and SMR were lower in group 1 compared with groups 2 (P < 0.001, P < 0.05), and 3 (P < 0.001); preoperative GCD was higher in group 1 compared with groups 2 and 3 (P < 0.001). DCD and GCD were also different between groups 2 and 3 (P < 0.05, P < 0.001). At 12 months, IOP reduced by 43.3%, 38.4%, and 15.8% in groups 1 to 3. Twelve-month IOP reduction negatively correlated with baseline DCD and SMR (P < 0.001, r = -0.786; P < 0.05, r = -0.618), and positively with GCD (P < 0.001, r = 0.752)., Conclusions: Preoperative DCD, GCD, and SMR are parameters correlated with the filtration surgery outcome, with DCD presenting the strongest correlation. IVCM of the conjunctiva may represent an imaging tool to predict the surgical success in glaucoma.

Background: to assess vessel density of superficial capillary plexus (SCP), deep capillary plexus (DCP) and choriocapillaris (CC) in advanced Stargardt disease (STGD) using optical coherence tomography angiography (OCTA) and correlate these findings with macular function using pattern electroretinogram (PERG) and multifocal electroretinogram (mfERG)., Methods: Twelve patients (24 eyes) with advanced STGD underwent vessel densities and macular thickness measurements using OCTA. A control group of 24 healthy controls (24 eyes) was chosen for comparison. In the STGD group correlation between vessel density and macular thickness and between macular function and morphologic parameters were evaluated., Results: Whole parafoveal vessel density (VD) of SCP was significantly lower in STGD group compared to the control group (p<0.05). Foveal VD and whole parafoveal VD of the DCP were significantly lower in STGD group compared to the controls (p<0.05). CC was significantly decreased in STGD compared to controls (p<0.05). Foveal macular thickness (MT), full parafoveal MT, and inner limiting membrane (ILM)-inner plexiform layer (IPL) parafoveal MT thickness were decreased in STGD eyes compared to controls (p<0.001). PERG and mfERG were both significantly reduced in STGD compared to controls (p<0.001). A direct correlation was found between full parafoveal MT and vessel density in the STGD group., Conclusions: Patients with advanced STGD showed a reduction of SCP, DCP and CC compared to healthy eyes related to a reduction of total and ILM-IPL macular thickness. These results suggest that both retinal capillaris plexuses and choriocapillaris reduction occur in STDG along with inner and outer retinal thinning., Competing Interests: The authors have declared that no competing interests exist.

The aim of this study is to determine modifications in stromal fluorescence intensity after different corneal cross-linking (CXL) procedures and to correlate stromal fluorescence to corneal biomechanical resistance. For confocal microscopy study, 15 human cadaver corneas were examined. Three served as control (group 1), three were just soaked with iontophoresis procedure (group 2), three were treated with standard epi-off technique (group 3), and six underwent iontophoresis imbibition. Three of later six were irradiated for 30 min with 3 mW/cm 2 UVA (group 4) and three for 9 min at 10 mW/cm 2 UVA (group 5). Confocal microscopy was performed to quantify the fluorescence intensity in the cornea at different stromal depths. For biomechanical study, 30 human cadaver corneas were randomly divided into five groups and treated as previously described. Static stress-strain measurements of the corneas were performed. Iontophoresis imbibition followed by 10mW/cm 2 irradiation proved to increase stromal fluorescence into the corneal stroma and significant differences were revealed between group 3 and 5 both at 100 (p = 0.0171) and 250 µm (p = 0.0024), respectively. Biomechanical analysis showed an improvement of corneal resistance in group 5. Iontophoresis imbibition followed by accelerated irradiation increased the stromal fluorescence and is related to an improvement of biomechanical resistance. This approach may represent a new strategy to achieve greater concentrations of riboflavin without removing corneal epithelium and improve clinical results while reducing the side effects of CXL.

Purpose: To investigate vessel changes occurring after aflibercept injections in treatment-naive exudative age-related macular degeneration patients., Methods: Fifteen eyes of 15 patients affected by wet age-related macular degeneration were enrolled in the study. All the patients had a diagnosis of Type 1 choroidal neovascularization and were treated with 3 monthly aflibercept intravitreal injections (IVI). Subjects were evaluated by means of optical coherence tomography angiography at baseline, the day after the first injection and one month after both the first and the second IVI. At last, all the patients were followed up to 2 months after the third IVI., Results: Foveal superficial vascular plexus flow density was 29.01% (21.13-37.32%) at baseline and was significantly reduced as soon as 1 month after the first IVI (median: 20.78%; interquartile range: 14.75-23.13%; P = 0.017). Parafoveal superficial vascular plexus flow density was 47.09% (44.91-51.72%) at baseline and significantly decreased as soon as 1 month after the second IVI (median: 44.40%; interquartile range: 41.59-49.29%; P = 0.034). Choroidal neovascularization lesion area remained stable throughout the follow-up. Nevertheless, interestingly, choroidal neovascularization flow area was significantly reduced as soon as the next day the first IVI (median: 0.37 mm and interquartile range: 0.27-0.72 mm at baseline; median: 0.30 mm and interquartile range: 0.24-0.64 mm at 1 day after the first IVI; P = 0.047)., Conclusion: Intravitreal aflibercept injections are associated with a significant change in native retinal and choroidal vasculature. Moreover, the treatment did not cause a reduction in lesion area, but rather reduced the flow in the choroidal neovascularization.

The aim of this study was to evaluate retinal and choriocapillaris vessel density using optical coherence tomography angiography (OCTA) in eyes with central retinal vein occlusion (CRVO) and branch retinal vein occlusion (BRVO) complicated by macular edema (ME). Sixty eyes of 60 patients with CRVO or BRVO and ME and 40 healthy subjects underwent measurements of superficial and deep foveal and parafoveal vessel density (FVD, PFVD) and choricapillary density using OCTA at baseline and 60 days after intravitreal dexamethasone implant (IVDEX). FVD and PFVD of the superficial plexus were not significantly lower in CRVO group compared to the controls while in the BRVO group overall PFVD were significantly lower compared to control group (p < 0.001). Overall PFVD of the deep plexus was significantly lower in CRVO and BRVO groups compared to the control group (p < 0.001). FVD and overall PFVD of choriocapillaris were significantly reduced compared to controls in CRVO group (p < 0.001) and PFVD of choriocapillaris was significantly reduced compared to controls in the affected hemi fields in BRVO groups (p < 0.001). OCTA showed vessel density reduction in BRVO and CRVO with main involvement of the deep retinal plexus compared to the superficial retinal plexus due to ischemia that did not recover after intravitreal dexamethasone implant.

The ciliary body ablation is still considered as a last resort treatment to reduce the intraocular pressure (IOP) in uncontrolled glaucoma. Several ablation techniques have been proposed over the years, all presenting a high rate of complications, nonselectivity for the target organ, and unpredictable dose-effect relationship. These drawbacks limited the application of cyclodestructive procedures almost exclusively to refractory glaucoma. High-intensity focused ultrasound (HIFU), proposed in the early 1980s and later abandoned because of the complexity and side effects of the procedure, was recently reconsidered in a new approach to destroy the ciliary body. Ultrasound circular cyclocoagulation (UC 3 ), by using miniaturized transducers embedded in a dedicated circular-shaped device, permits to selectively treat the ciliary body in a one-step, computer-assisted, and non-operator-dependent procedure. UC 3 shows a high level of safety along with a predictable and sustained IOP reduction in patients with refractory glaucoma. Because of this, the indication of UC 3 was recently extended also to naïve-to-surgery patients, thus reconsidering the role and timing of ciliary body ablation in the surgical management of glaucoma. This article provides a review of the most used cycloablative techniques with particular attention to UC 3 , summarizing the current knowledge about this procedure and future possible developments.

Aims: To evaluate, using anterior segment optical coherence tomography (AS-OCT) and in vivo confocal microscopy (IVCM), the uveo-scleral aqueous humour (AH) outflow pathways after ultrasonic circular cyclocoagulation (UCCC)., Methods: Forty-four patients with refractory glaucoma underwent 4 or 6 s UCCC (group 1, 24 eyes; group 2, 20 eyes). UCCC was successful when the preoperative intraocular pressure (IOP) reduced by one-third. AS-OCT and IVCM were performed at baseline and at month 1 to evaluate the sclera and conjunctiva. The main outcomes were mean intra-scleral hyporeflective spaces area (MIHSA: mm 2 ) at AS-OCT, mean density and area of conjunctival microcysts (MMD: cysts/mm 2 ; MMA: µm 2 ) at IVCM. The relations between MIHSA, MMA and MMD with IOP were analysed., Results: Mean baseline IOP was 26.9±2.8 mm Hg in group 1 and 27.5±4.0 in group 2. Intra-scleral hyporeflective spaces and microcysts were observed in both groups, without significant differences in MIHSA, MMA and MMD. At month 1, UCCC was successful in 63.6% of patients (41.6% in group 1, 80% in group 2), and IOP reduced to 18.8±3.2 (30.1%) and 17.1±2.7 mm Hg (38.7%), respectively (p<0.001). MIHSA showed a twofold and threefold increase in group 1 and 2 (p<0.05), with a significant difference between groups (p<0.05). MMA and MMD increased in both groups (p<0.05), with values higher in group 2 (p<0.05). Significant relations were found between MIHSA and IOP in both groups (p<0.01)., Conclusions: UCCC induced anatomical modifications of sclera and conjunctiva, which suggested that the trans-scleral AH outflow enhancement is one of the possible mechanisms exploited by ultrasounds to reduce IOP., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.)

Purpose: The purpose of this study was to evaluate dendritic cell (DC) distribution, morphology, and DC density in the entire cornea of medically controlled glaucoma patients (MCGP), using in vivo confocal microscopy (IVCM)., Methods: Fifty MCGP were enrolled, 15 patients with dry eye, and 15 healthy subjects served as controls. Patients were asked to complete the Ocular Surface Disease Index (OSDI) questionnaire and then underwent tear film break-up time (BUT), corneal staining, and Schirmer test (ST) I and then IVCM. In vivo confocal microscopy evaluated the limbal and central DC density, the DCs morphology and distribution. Relationships among DC density, OSDI score, and corneal staining were analyzed., Results: Medically controlled glaucoma patients were divided into 2 groups; group 1 (29 eyes) was tested with one drug; group 2 (21 eyes) was tested with ≥2 drugs. Dendritic cells were significantly higher at limbus than at central cornea in both groups. Limbal DCs were found in the 86.7%, 89.7%, 90.4%, and 93.3% of eyes in controls, groups 1 and 2, and DED; central corneal DCs were found in the 26.6%, 75.9%, 80.9%, and 86.6% of eyes in controls, groups 1 and 2, and DED. Dendritic cell density was higher in glaucoma groups and DED than in controls (P < 0.001). Group 2 and DED presented DC density significantly higher compared with group 1 (P < 0.05). In group 1 DC density was higher in patients taking preserved drugs than in those taking preservative-free drugs (P < 0.05). Dendritic cell density was higher in DED than in group 2 (P < 0.05). Dendritic cell density significantly correlated with corneal staining and OSDI (P < 0.001)., Conclusions: Dendritic cells increase in the entire cornea of MCGP, with a higher density at limbus. These modifications may take part in the induction of the glaucoma-related ocular surface disease.

Purpose: To investigate correlations among macular ganglion cell complex (GCC) layer thickness, macular capillary density, and macular function in patients affected by retinitis pigmentosa (RP)., Methods: Fourteen patients (28 eyes) with previous diagnosis of RP were enrolled. The diagnosis of these conditions was made based on both clinical features and electrophysiological examination. All patients underwent a complete ophthalmologic examination, including optical coherence tomography angiography (OCTA) and multifocal electroretinogram (mfERG). Main outcome measures were macular GCC layer thickness; superficial capillary plexus (SCP) vessel density; deep capillary plexus (DCP) vessel density; choriocapillaris plexus (CCP) vessel density; and amplitudes of mfERG N1 and P1 waves., Results: Average GCC thickness was significantly thinner in RP patients (76.0 ± 25.1 and 109.2 ± 17.5 μm, P = 0.028). Superficial capillary plexus density was 42.2 ± 3.4% in the RP group and 51.4 ± 2.3% in the control group (P < 0.001). Deep capillary plexus density was reduced in RP patients (42.7 ± 6.2%) after the comparison with healthy subjects (56.6 ± 2.2%, P < 0.001). Choriocapillaris plexus density was significantly less in RP patients than in the control group (65.3 ± 2.7% and 67.2 ± 1.4%, P = 0.024). Superficial capillary plexus and DCP density were significantly correlated with both mfERG values and GCC thickness., Conclusions: We showed that both choroid and retinal vessels were modified in RP patients after comparison with healthy subjects. Moreover, we demonstrated that the SCP and DCP vessel densities are correlated with the macular function, as well as with the GCC thickness.

Purpose: To investigate alteration in superficial and deep retinal vascular densities and choroidal thickness, in patients affected by early and intermediate age-related macular degeneration (AMD)., Methods: All patients had undergone optical coherence tomography angiography (OCTA). All eyes were grouped into two stages: "early AMD" and "intermediate AMD." Outcome measures were superficial vessel density, deep vessel density, and choroidal thickness. A control group of healthy subjects was selected for the statistical comparisons., Results: A total of 37 eyes of 37 dry AMD patients were enrolled for the study. Fourteen of 37 eyes were classified as having early AMD, the remaining 23 of 37 eyes were classified as being affected by intermediate AMD. Superficial and deep vessel densities were 39.21% ± 10.67% and 43.84% ± 11.57%, respectively, in the control group and 28.30% ± 10.73% and 36.41% ± 12.30%, respectively, in AMD patients (P = 0.001 and P = 0.017, respectively). Choroidal thickness was significantly reduced in AMD patients., Conclusion: In the last years, several studies have reported vascular factors playing an important role in AMD pathogenesis. We demonstrated that both superficial and deep retinal plexuses are altered among patients affected by AMD. Interestingly, this alteration starts immediately at the intermediate AMD stage and also the choroidal thickness reduction.

Purpose: To describe the variable ocular phenotype associated with a heterozygous mutation in the BEST1 gene., Methods: Clinical and genetic assessment was performed in five members of the same family. Molecular genetic analysis of the BEST1 gene was performed by direct sequencing. Extensive ophthalmic examination included color fundus imaging, spectral domain optical coherence tomography, fundus autofluorescence, electro-oculography (EOG), and full-field electroretinography (ERG). The main outcome measures were BEST1 mutations, imaging, and electroretinography findings., Results: All affected family members carried a single heterozygous c.614T>C (p.I205T) mutation in exon 5 of the BEST1 gene. The 46-year-old proband showed nanophthalmos with chorioretinal atrophy in the macula, extensive coarse hyperpigmentation in the (mid) peripheral retina with tractional vitreous strands. Full-field ERG revealed nonrecordable cone and rod responses, and EOG showed an absent light rise. The daughter and son of the proband showed a phenotype resembling autosomal recessive bestrophinopathy, including short axial lengths, cystoid fluid collections, and shallow serous subretinal fluid accumulation on spectral domain optical coherence tomography throughout the macula in combination with mild retinal pigment epithelium changes. The son of the proband also showed subretinal yellowish deposits inferiorly in the macula as well as outside the temporal vascular arcade, that were hyperfluorescent on fundus autofluorescence, similar to those seen in autosomal recessive bestrophinopathy. Full-field ERG revealed a reduced rod and cone response and a markedly reduced or absent EOG light peak in both brother and sister of the proband., Conclusion: The clinical spectrum of bestrophinopathy may encompass severe ocular phenotypes that affect the development and function of the entire eye. A clinical picture similar to autosomal recessive bestrophinopathy can also be caused by a single heterozygous mutation in the BEST1 gene, such as the c.614T>C (p.I205T) variant in this family.

Purpose: To report morphologic features of idiopathic macular telangiectasia (MacTel) type 2 by means of optical coherence tomography angiography (OCTA) and to compare these findings to fundus fluorescein angiography (FFA), fundus autofluorescence (FAF), confocal blue reflectance (CBR), and spectral-domain OCT (SD-OCT). In addition, foveal vessel density and parafoveal vascular density (PFVD), and foveal retinal thickness and parafoveal retinal thickness (PFRT) were compared between MacTel 2 patients and normal aged-matched controls., Methods: Eight patients (15 eyes) with MacTel 2 and 17 normal controls (17 eyes) underwent retinal multimodal imaging assessment and grading. Results from different imaging techniques were used to compare interimaging modalities. Objective quantification of retinal vessel density and macular thickness was evaluated in MacTel 2 patients (15 eyes)., Results: In MacTel 2 eyes a comparison of OCTA to the other imaging techniques showed that the strongest correlations were present with SD-OCT, early FFA, and late FFA. Moderate correlations were found between OCTA and CBR and FAF. Foveal vessel density was significantly lower in MacTel 2 eyes than control eyes both in the superficial plexus (23.74% vs. 33.14%; P = 0.003) and in the deep plexus (24.63% vs. 34.21%; P = 0.005). Superficial PFVD was significantly different in the two groups (47.06% vs. 51.40%; P = 0.005) but not the deep PFVD. Foveal retinal thickness was 214.13 μm in MacTel 2 eyes and 258.18 μm in normal controls, and PFRT was 279.60 and 323.29 μm, respectively (P < 0.0001)., Conclusions: Optical coherence tomography angiography is useful for retinal vasculature characterization in MacTel type 2 patients and showed a high correlation with well-established imaging techniques.

Purpose: To evaluate and compare the clinical outcomes with an aspheric monofocal intraocular lens (IOL) and an extended range of vision (ERV) IOL based on achromatic diffractive technology., Methods: This was a prospective comparative study including 80 eyes undergoing cataract surgery with implantation of the monofocal Tecnis ZCB00 IOL (Abbott Medical Optics Inc., Santa Ana, CA) (monofocal group: 30 eyes of 15 patients) or the ERV Tecnis Symfony IOL (Abbott Medical Optics, Inc.) (ERV group: 50 eyes of 25 patients). Visual, refractive, contrast sensitivity, defocus curve, ocular optical quality (Optical Quality Analysis System; Visiometrics SL, Terrassa, Spain), and quality of life (National Eye Institute Refractive Error Quality of Life Instrument 42 Questionnaire) outcomes were evaluated during a 3-month follow-up., Results: Significantly better postoperative uncorrected monocular and binocular distance (UDVA), intermediate (UIVA), and near (UNVA) visual acuities were found in the ERV group (P ≥ .013). Postoperative spherical equivalent was within ±1.00 diopters in 94% and 100% of eyes in the ERV and the monofocal groups, respectively. Binocular UIVA and UNVA of 0.20 or better (Snellen 20/30) were observed in all cases in the ERV group and in 13.3% and 6.7% of eyes of the monofocal group, respectively. No significant differences among groups were observed in contrast sensitivity (P ≥ .156) or ocular optical quality parameters (P ≥ .084). In the monocular defocus curve, all visual acuities were better in the ERV group (P ≤ .002), except for the +0.50-diopter defocus level (P = .367). Significantly better scores were obtained for dependence on correction (P = .003) and suboptimal correction (P = .038) subscales in the ERV group., Conclusions: The extended range of vision IOL provides better distance, intermediate, and near visual acuity than the aspheric monofocal IOL, while maintaining the same level of visual quality. [J Refract Surg. 2016;32(7):436-442.]., (Copyright 2016, SLACK Incorporated.)

Purpose: We analyzed the preoperative conjunctival goblet cell density (GCD), MUC5AC, and HLA-DR in glaucomatous patients undergoing trabeculectomy, using laser scanning confocal microscopy (LSCM) and impression cytology (IC)., Methods: We enrolled 57 patients undergoing trabeculectomy. At baseline LSCM and IC were performed at the site planned for surgery; LSCM was repeated after 12 months at the bleb site. The main outcomes were: GCD, mean microcyst density (MMD) and area (MMA) at LSCM, MUC5AC, and HLA-DR positivity at IC, and IOP. The relationships between baseline GCD, and 12-month IOP, MMD, and MMA were analyzed., Results: Trabeculectomy was successful in 39 patients (complete success in 27, Group 1; qualified in 12, Group 2), and unsuccessful in 18 (Group 3). At baseline IOP (mm Hg) was 27.2 ± 3.12, 27.5 ± 2.23, and 27.7 ± 1.90 in Groups 1 to 3, respectively; GCD and MUC5AC positivity were higher in Group 1 compared to Groups 2 and 3 (P < 0.05); HLA-DR, MMD, and MMA were not significantly different among the groups. At 12 months, IOP reduced by 45.3%, 35.4%, and 12.8% in Groups 1 to 3, respectively. Goblet cell density did not change in Group 1, whereas it was reduced in Groups 2 and 3 (P < 0.05), with values lower in Group 3. Mean microcyst density and MMA increased in Groups 1 and 2 (P < 0.05), with values higher in Group 1 (P < 0.05). Baseline GCD positively correlated with 12-month IOP reduction (P < 0.001, r = 0.641), MMD (P < 0.05, r = 0.454), and MMA (P < 0.001, r = 0.541)., Conclusions: Goblet cells positively affect the filtration ability after trabeculectomy; therefore, preoperative GCD could be considered as a potential in vivo biomarker of surgical success.

Background/aims: To assess the reproducibility and repeatability of foveal avascular zone (FAZ) area measurements using optical coherence tomography angiography (OCT-A) in healthy subjects., Methods: Sixty healthy volunteers (60 eyes) were subjected to FAZ area measurements by means of high speed and high resolution spectral-domain OCT (SD-OCT) XR Avanti with the split-spectrum amplitude decorrelation angiography algorithm by two experienced examiners in two different sessions., Results: The mean±SD age of the subjects was 28.9±7.6 years. Overall FAZ areas measured by the first and second observer were 0.251±0.096 mm(2) and 0.252±0.096 mm(2), respectively. Within subjects, the coefficients of variations were 1.83% (95% CI 1.51% to 2.20%) and 1.86% (95% CI 1.33% to 2.43%) for the first and second observers, respectively. The coefficient of repeatability average measurements of FAZ area were 0.015 mm(2) and 0.013 mm(2) for the first and second observers, respectively. The intraclass correlation coefficient values were 0.997 (95% CI 0.995 to 0.998) and 0.998 (95% CI 0.996 to 0.999) for the first and second observers, respectively. Inter- and intraobserver concordance correlation coefficients ranged from 0.994 (95% CI 0.990 to 0.977) to 0.999 (95% CI 0.997 to 0.999) and from 0.997 (95% CI 0.995 to 0.998) to 0.996 (95% CI 0.994 to 0.998), respectively., Conclusions: FAZ area measurements by means of OCT-A showed excellent reproducibility and repeatability in healthy eyes. OCT-A is a non-invasive diagnostic method, and its reliability makes it an interesting potential diagnostic tool for disease detection and follow-up in retinal pathologies involving foveal microcirculation., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)

This retrospective quality control study aimed at comparing resolution in patients treated with intravitreal ocriplasmin (IVO) using two injection techniques, classical injection procedure (unguided) and targeted injection using a surgical microscope with a 30-gauge 1-inch needle (guided) for the treatment of focal VMT without macular hole. The two groups presented a statistically significant difference in terms of resolution of VMT within the first month following treatment: 1/7 for the unguided group versus 6/7 for the guided group (p = 0.0291). The majority of the guided group presented an earlier resolution than the single resolved case in the unguided group. The results of this preliminary study indicate that the injection of ocriplasmin closer to the site of VMT results in the resolution in a higher number of cases and that this resolution occurs in a short time interval.

Meibomian glands (MGs) play a crucial role in the ocular surface homeostasis by providing lipids to the superficial tear film. Their dysfunction destabilizes the tear film leading to a progressive loss of the ocular surface equilibrium and increasing the risk for dry eye. In fact, nowadays, the meibomian gland dysfunction is one of the leading causes of dry eye. Over the past decades, MGs have been mainly studied by using meibography, which, however, cannot image the glandular structure at a cellular level. The diffusion of the in vivo laser scanning confocal microscopy (LSCM) provided a new approach for the structural assessment of MGs permitting a major step in the noninvasive evaluation of these structures. LSCM is capable of showing MGs modifications during aging and in the most diffuse ocular surface diseases such as dry eye, allergy, and autoimmune conditions and in the drug-induced ocular surface disease. On the other hand, LSCM may help clinicians in monitoring the tissue response to therapy. In this review, we summarized the current knowledge about the role of in vivo LSCM in the assessment of MGs during aging and in the most diffuse ocular surface diseases.

Background: To investigate changes in macular morphology and function after an intravitreal dexamethasone implant for diabetic macular edema (DME)., Methods: Twenty-seven eyes in 27 treatment-naive patients affected by DME were treated with intravitreal Ozurdex® injections (IVOI) and followed up 12 months to evaluate morphological and functional changes by means of best-corrected visual acuity (BCVA), microperimetry (MP1), multifocal electroretinography (mfERG), pattern electroretinography (PERG) and spectral domain optical coherence tomography (SD-OCT)., Results: Both BCVA and retinal sensitivity improved significantly at one month after the IVOI (p = 0.031 and p<0.0001, respectively). After five months, the improvement of BCVA remained statistically significant compared with baseline values (p = 0.022); retinal sensitivity improvement was statistically significant for up to four months after the IVOI (p = 0.059). Moreover, central macular thickness significantly decreased for up to four months. Interestingly, PERG and mfERG values did not change significantly for up to four months post-IVOI, but then began to worsen., Conclusions: In eyes with DME, intravitreal dexamethasone implant determined morphological and functional improvement as soon as one month and for up to four months after the treatment.

Purpose: To assess the clinical usefulness of chorioretinal biopsy in establishing a definitive diagnosis in intraocular lymphomas., Design: Retrospective, noncomparative, consecutive diagnostic case series., Methods: setting: Moorfields Eye Hospital, London, United Kingdom., Patients: Twenty-nine consecutive patients presenting with severe uveitis that required an intraocular biopsy where underlying lymphoma was suspected., Observation Procedure: A retrospective review of a 15-year period (1999-2014) was undertaken of all patients that have undergone chorioretinal biopsy for suspected lymphoma at Moorfields Eye Hospital, London, United Kingdom. Patients were identified on the hospital's computerized database., Main Outcome Measures: Effectiveness of chorioretinal biopsy in establishing a definitive diagnosis or in excluding malignancy., Results: A specific histologic diagnosis was made in 17 cases (59%) while in 9 cases the biopsy combined with clinical data was effective in excluding malignancy. In the 3 remaining cases, no specific diagnosis was made. No intraoperative complications were reported. Postoperative complications other than cataract included 2 vitreous hemorrhages and 2 retinal detachments. Of the 17 cases with a histologic diagnosis, 15 were obtained in eyes with marked vitritis, as opposed to 2 with minimal vitritis., Conclusions: Chorioretinal biopsy provided a definitive diagnosis of lymphoma in 59% of cases and assisted in exclusion of a further 31% in this series. The level of vitritis appears to act as a strong index of likelihood in achieving a definitive histologic diagnosis., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Purpose: To evaluate intraocular lens (IOL) axial movements and refractive changes during a 6-month follow-up period after femtosecond laser-assisted cataract surgery and conventional cataract surgery, investigate the influence of capsulorhexis features on postoperative IOL axial changes, and assess the prediction error for both techniques., Methods: Eighty eyes of 80 candidates for cataract extraction were randomized into two groups: femtosecond laser (40 eyes) and manual (40 eyes)., Results: The overall anterior chamber depth variation was significantly lower in the femtosecond laser group compared to the manual group during follow-up (P<.001). At 30 and 180 days postoperatively, the mean spherical equivalent showed a hyperopic shift (0.09±0.28 diopters [D]) in the femtosecond laser group and a myopic shift in the manual group (-0.25±0.18 D). Median absolute error was not significantly different between the two groups with standard formulas ranging between 0.29 and 0.64 (Hoffer Q) in the femtosecond laser group and between 0.24 (SRK-T) and 0.55 D (Hoffer Q) in the manual group. There was a significant lower deviation from intended versus achieved capsulotomy/capsulorhexis area in the femtosecond laser group (P<.001) compared to the manual group. The femtosecond laser group showed better IOL centration compared to the manual group at all time periods (P<.001)., Conclusions: Femtosecond laser-assisted cataract surgery was related to a lower overall variability of anterior chamber depth compared to conventional cataract surgery with more stable postoperative refraction. The two techniques did not show significant differences of prediction error., (Copyright 2015, SLACK Incorporated.)

Purpose: To correlate clinical, impression cytologic, and in vivo confocal microscopy findings on the corneal surface after cultured limbal stem cell transplantation., Design: Prospective, interventional, noncomparative, masked case series., Participants: Thirteen patients with limbal stem cell deficiency after unilateral (9 eyes) or bilateral (2 eyes) chemical burn, liquid nitrogen injury (1 eye), or herpes simplex virus infection (1 eye)., Methods: Limbal cells were harvested from healthy or less affected eyes, cultured on 3T3 cells and fibrin glue, and transplanted to the patient's injured eye. Patients underwent clinical examination and impression cytologic examination of the central cornea before and 1 year after intervention. In vivo confocal microscopy scans were obtained in all corneal quadrants after 1 year. The interexamination agreement was established by calculation of the Cohen's κ coefficient., Main Outcome Measures: Results of surgery were assessed considering clinical signs (successful: restoration of transparent, avascular, and stable corneal epithelium without neovascularization in central corneal surface; partially successful: recurrence of superficial neovascularization; failed: recurrent epithelial defects, pannus, and inflammation), phenotype of cells covering the corneal surface (conjunctivalized corneal surface: cytokeratin 12 [cK12]-negative and mucin 1 [MUC1]-positive cells; mixed epithelium: cK12-positive and MUC1-positive cells; corneal epithelium: cK12-positive and MUC1-negative cells), and cell morphologic features (corneal epithelium: multilayered polygonal and flat cells with hyperreflective nuclei; conjunctival epithelium: stratified cuboidal or polygonal cells, hyperreflective cytoplasm, and barely defined borders; epithelial transition: transition of epithelial cells from the cornea to the conjunctiva over the corneal surface)., Results: We found a moderate to substantial degree of concordance between confocal microscopy and clinical evaluation (κ = 0.768) and between confocal microscopy and impression cytologic analysis (κ = 0.629). Confocal microscopy showed that 46.2% of patients exhibited corneal epithelium in the central and peripheral cornea, 30.8% showed an irregular mixed corneal and conjunctival epithelium, and 23.0% showed conjunctival epithelium. Palisades of Vogt were absent in all (100.0%) patients, and the cornea-conjunctiva epithelial transition localized approximately 1 mm internally on the cornea., Conclusions: Confocal microscopy provides objective measures of the corneal epithelium and may significantly improve the evaluation of outcomes after cultured limbal stem cell graft., (Copyright © 2015 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Aims: To investigate aqueous humour changes in vascular endothelial growth factor (VEGF) and pigment epithelium-derived factor (PEDF) levels in patients with choroidal neovascularisation (CNV) secondary to pathological myopia (mCNV) before and after intravitreal ranibizumab injection (IVR)., Methods: This was a prospective, case-control study investigating aqueous levels of VEGF and PEDF in eyes with mCNV treated with IVR., Results: Mean VEGF and PEDF levels in the aqueous humour of control patients were 25.7±4.9 pg/mL and 12.6±3.5 ng/mL, respectively. Lower levels of both VEGF (19.5±5.4 pg/mL) and PEDF (4.7±2.2 ng/mL) were found in patients with mCNV before IVR. After IVR, aqueous VEGF levels significantly reduced to 6.5±2.7 pg/mL, while PEDF levels significantly increased to 35.8±11.4 ng/mL. VEGF and PEDF levels significantly correlated with each other, and with best-corrected visual acuity and central retinal thickness., Conclusions: The VEGF and PEDF levels in aqueous humour were significantly lower in the myopic group than in controls. Moreover, IVR resulted in reduced VEGF and increased PEDF levels in patients with mCNV. In mCNV, neovascularisation is associated with inappropriate VEGF and PEDF expression. A balance between VEGF and PEDF is crucial to prevent CNV development., Trial Registration Number: NCT02175940., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Purpose: The aims of this study are to investigate the expression of leucine-rich repeat-containing G protein-coupled receptor 5 (LGR5) protein in the normal human cornea and limbus and to analyze modifications of this expression under inflammatory conditions., Methods: The expression of LGR5 was evaluated in seven limbal epithelial crypts (LECs), collected from healthy cadaver donors, and five inflamed LECs obtained from enucleated eyes. Central corneal buttons were used as controls. LGR5 protein distribution was determined by immunohistochemistry staining analysis., Results: The cytoplasmic expression of LGR5 protein was observed in 100% of healthy LECs. Three out of five inflamed tissues analyzed were completely negative, while in the two remaining cases, we observed a moderate positivity in the basal cells of LECs. No relation was found between the expression of LGR5 and the grade of inflammatory cells., Conclusions: These findings demonstrate the presence of LGR5-positive cells in human LECs and their decrease in inflamed conditions, which suggests a critical role of this protein during inflammation and its possible use as a marker in normal crypts.

Purpose: To evaluate the visual outcome, spectacle independence, and patient satisfaction after implantation of two Acrysof ReSTOR (Alcon Laboratories, Inc., Fort Worth, TX) intraocular lenses (IOLs) with different addition power or their combination in both eyes., Methods: One hundred twenty eyes of 60 patients with bilateral multifocal IOL implantation were divided into three groups of 20 consecutive patients each: the SV25T0 (the T0 group), the SN6AD1 (the D1 group), or a combination of both the SN6AD1 and SV25T0 (the combined group). Patients were observed 18 months postoperatively for visual acuity (40, 50, and 60 cm, and 4 m), defocus curves (range: +1.0 to -4.0 diopters), and contrast sensitivity. Quality of vision, patient satisfaction, and spectacle independence were evaluated by the National Eye Institute Refractive Error Quality of Life Instrument-42 questionnaire., Results: The D1 group achieved better results for near vision (P < .01), whereas the T0 group achieved better intermediate vision (P = .01). The combined group showed a wider range of spectacle independence at all distances evaluated (P < .05). The contrast sensitivity was similar within the groups. The incidence of glare was lower for the T0 group (P = .054). The combined group had better results in terms of expectation (P = .021) and activity limitation (P = .003)., Conclusion: Although the bilateral implantation of the same multifocal IOL can maximize the vision for near or intermediate distances, the combination of these IOLs in both eyes can increase the range of spectacle independence without compromising the contrast sensitivity and quality of vision., (Copyright 2015, SLACK Incorporated.)

Purpose: To investigate morphologic changes of the corneoscleral limbus in glaucoma patients using laser scanning confocal microscopy (LSCM) and impression cytology (IC)., Methods: Eighty patients with glaucoma and 20 with dry eye were enrolled; 20 healthy subjects served as controls. Patients underwent the Ocular Surface Disease Index (OSDI) questionnaire, tear film break-up time, corneal staining, Schirmer test I, and LSCM of the limbus. Laser scanning confocal microscopy evaluated the limbal transition epithelium (LTE) regularity, dendritic cell (DC) density, and palisades of Vogt (POV). Impression cytology was performed and samples stained with HLA-DR and IL6., Results: Glaucomatous patients were divided into three groups: Group 1 (40 eyes): one drug; Group 2 (20): two drugs; and Group 3 (20): three or more drugs. Limbal transition epithelium regularity was worse, and DC density higher in Groups 2, 3, and dry eyes compared with Group 1 and controls (P < 0.01). Preserved drugs worsened LTE regularity and induced higher DC density compared with preservative-free (PF) drugs (P = 0.041; P = 0.004). Despite typical POV architecture was preserved, signs of inflammation were found in glaucoma groups. HLA-DR and IL-6 positivity were higher in Groups 2, 3, and dry eye compared with controls (P < 0.001), and in preserved versus PF drugs (P < 0.05; P < 0.001). Dendritic cell density and LTE regularity correlated with HLA-DR, IL-6, and OSDI score in glaucoma groups and dry eyes (P < 0.001)., Conclusions: Laser scanning confocal microscopy and IC documented antiglaucoma therapy induced morphologic alterations of limbus, which may play a role in the glaucoma-related ocular surface disease. Further studies are required to determine if limbal changes affect stem cell viability., (Copyright 2015 The Association for Research in Vision and Ophthalmology, Inc.)

Aim: To investigate the features of optic nerve head (ONH) microvasculature in primary open angle glaucoma using fractal geometry analysis., Patients and Method: ONH blood flow was analyzed at the level of the lamina cribrosa by means of confocal scanning laser Heidelberg Doppler flowmetry (HRF) in medically-controlled early and advanced glaucoma. Fractal dimension D of vasculature map was calculated using the Box Counting., Results: Our data demonstrated that, in patients with advanced glaucoma, fractal dimension D was significantly lower than in controls, whereas, in the early stage of disease, its value was similar. Fractal dimension D of microcirculation was significantly and negatively correlated with the cup-disk area ratio in both early and advanced glaucoma groups, whereas linear cup-disk ratio of the disk, cup shape measure and nerve fiber layer thickness, where correlated only in advanced stage of the disease., Conclusion: These findings demonstrate that fractal dimension D of ONH appeared significantly reduced in advanced glaucoma and correlated with the optic disc damage., (Copyright © 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)

Purpose: To examine the circadian intraocular pressure (IOP) patterns in healthy subjects, in primary open angle and normal tension glaucoma (POAG; NTG) using a contact lens sensor (CLS; Sensimed Triggerfish, Lausanne, Switzerland)., Methods: This was an observational, nonrandomized study. Ten healthy subjects (Group 1, 10 eyes) and 20 glaucomatous patients [20 eyes, 10 with POAG (Group 2) and 10 with NTG (Group 3)] were enrolled. All patients were controlled with prostaglandin analogues. The 24-hr IOP pattern was the main outcome. The morning (6AM-11AM), afternoon/evening (noon-11PM) and night (midnight-5AM) subperiod patterns, peaks and prolonged peaks (>1 hr) were secondary outcomes., Results: Mean 24-hr IOP pattern showed a nocturnal acrophase in all groups. Patterns were significantly different among groups (p = 0.02), with highest nocturnal IOP values in POAG. Prolonged peaks were more common in patients with glaucoma (70%) than in healthy subjects (33.3%) (p < 0.001). Significant differences were found for Groups 2 and 3 in the morning versus afternoon/evening (p = 0.019 and p = 0.035, Bonferroni correction), morning versus night (p = 0.005 and p < 0.0001) and afternoon/evening versus night periods comparisons (p < 0.0001 for both groups). In Group 1, patterns significantly differed in the morning versus night and afternoon/evening versus night period comparisons (p < 0.0001)., Conclusions: Continuous 24-hr IOP monitoring with the CLS revealed a nocturnal acrophase in healthy subjects and, more markedly, in glaucoma. Because the diurnal IOP profile seems not to predict the nocturnal rhythm, the circadian IOP pattern should be evaluated in clinical practice. These findings may be worthwhile for the management of glaucoma., (© 2014 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

Purpose. To assess the ability of optical coherence tomography-angiography (OCT-A) to show and analyze retinal vascular patterns and the choroidal neovascularization (CNV) in retinal vascular diseases. Methods. Seven eyes of seven consecutive patients with retinal vascular diseases were examined. Two healthy subjects served as controls. All eyes were scanned with the SD-OCT XR Avanti (Optovue Inc, Fremont CA, USA). Split spectrum amplitude decorrelation angiography algorithm was used to identify the blood flow within the tissue. Fluorescein angiography (FA) and indocyanine green angiography (ICGA) with Spectralis HRA + OCT (Heidelberg Engineering GmbH) were performed. Results. In healthy subjects OCT-A visualized major macular vessels and detailed capillary networks around the foveal avascular zone. Patients were affected with myopic CNV (2 eyes), age-related macular degeneration related (2), branch retinal vein occlusion (BRVO) (2), and branch retinal artery occlusion (BRAO) (1). OCT-A images provided distinct vascular patterns, distinguishing perfused and nonperfused areas in BRVO and BRAO and recognizing the presence, location, and size of CNV. Conclusions. OCT-A provides detailed images of retinal vascular plexuses and quantitative data of pathologic structures. Further studies are warranted to define the role of OCT-A in the assessment of retinovascular diseases, with respect to conventional FA and ICG-A.

Glaucoma is a multifactorial disease that is the leading cause of irreversible blindness. Recent data documented that glaucoma is not limited to the retinal ganglion cells but that it also extends to the posterior visual pathway. The diagnosis is based on the presence of signs of glaucomatous optic neuropathy and consistent functional visual field alterations. Unfortunately these functional alterations often become evident when a significant amount of the nerve fibers that compose the optic nerve has been irreversibly lost. Advanced morphological and functional magnetic resonance (MR) techniques (morphometry, diffusion tensor imaging, arterial spin labeling, and functional connectivity) may provide a means for observing modifications induced by this fiber loss, within the optic nerve and the visual cortex, in an earlier stage. The aim of this systematic review was to determine if the use of these advanced MR techniques could offer the possibility of diagnosing glaucoma at an earlier stage than that currently possible.

Normal-tension glaucoma (NTG) is a multifactorial disease where mechanical stresses and vascular alterations to the optic nerve head probably represent the key pathogenic moments. Although intraocular pressure (IOP) plays a crucial role in the retinal ganglion cell loss, the IOP reduction does not necessarily reduces the disease progression. Therefore, several IOP-independent factors such as glutamate toxicity, oxidative stress, autoimmunity, and vascular dysregulation have been considered in the pathogenesis of NTG. Numerous evidences documented an impairment of the ocular blood flow, involved both in the onset and progression of the disease. The IOP reduction remains the main strategy to reduce the damage progression in NTG. Recently, new treatment strategies have been proposed to improve the control of the disease. Neuroprotection is a rapidly expanding area of research, which represents a promising tool. In the present review, we summarize the recent scientific advancements in the pathogenesis and treatment of NTG., (© 2015 Elsevier B.V. All rights reserved.)

Purpose: To evaluate monocular functional outcomes after the implantation of the AcrySof ReSTOR SN6AD2 intraocular lens (IOL) (+2.5 diopters [D] near add) (Alcon Laboratories, Inc., Fort Worth, TX) and the AcrySof ReSTOR SN6AD1 IOL (+3.0 D near add) (Alcon Laboratories, Inc.)., Methods: This prospective, comparative, nonrandomized single-blind observational study comprised 62 eyes of 62 patients that underwent phacoemulsification and implantation of a multifocal IOL: SN6AD2 (31 eyes) (+2.5 group) and SN6AD1 (31 eyes) (+3.0 group). Twelve months after surgery, monocular near (30 and 40 cm), intermediate (50, 60, and 70 cm), and distance (4 m) visual acuity were evaluated with the internal root mean square and modulation transfer function. Both parameters were evaluated at the 4- and 6-mm pupil sizes., Results: No statistical differences at 4 m were found between the groups. The +2.5 group obtained better performances at all intermediate distances (50 cm, 0.23 ± 0.14 vs 0.32 ± 0.13; 60 and 70 cm, 0.21 ± 0.10 vs 0.41 ± 0.14 and 0.24 ± 0.10 vs 0.53 ± 0.17, respectively), whereas the near visual acuity was better for the +3.0 group (30 and 40 cm, 0.36 ± 0.18 vs 0.14 ± 0.09 and 0.36 ± 0.19 vs 0.17 ± 0.07, respectively). The root mean square was lower for the +2.5 group compared to the +3.0 group, whereas the modulation transfer function showed overlapping results between the two models., Conclusions: Both IOL models showed good results in distance vision; the +2.5 D IOL seemed to provide better intermediate vision than the +3.0 D IOL. For near vision, the +3.0 D model performed better than the +2.5 D model., (Copyright 2014, SLACK Incorporated.)

Diabetic retinopathy (DR) is the leading cause of vision loss in the working-age adults. It affects a third of diabetics. Diabetic macular edema, an advanced complication of DR, develops in nearly 7% of diabetic patients. MicroRNAs (miRNAs) are a novel group of non-coding small RNAs that post-transcriptionally control gene expression by promoting either degradation or translational repression of target messenger RNA. They are implicated in a large variety of physiological and pathophysiological processes, including glucose homeostasis, angiogenesis and modulation of inflammatory response. MiRNAs also play a critical role in the pathogenesis of diabetes and the related micro- and macrovascular complications. The purpose of this review is to describe the potential role of miRNAs in diabetes and evaluate their implication in DR. MiRNAs involved in the modulation of glucose metabolism (insulin secretion and sensitivity) and MiRNAs playing a role in the pathogenesis of DR with their potential target genes are reviewed. Understanding MiRNAs implication in DR could be helpful for developing new gain- or loss- of -function strategies in order to establish effective treatments and reduce the rate of visual disability due to progression of retinopathy., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Purpose: To analyze, using in vivo laser scanning confocal microscopy (LSCM), the conjunctival features in glaucomatous patients receiving prostaglandin analogues (PGA)., Methods: Eighty eyes of 80 consecutive glaucomatous patients naive for therapy were enrolled; 30 eyes of 30 healthy subjects served as a control. Patients were randomized to: preservative-free (PF) and preserved latanoprost (groups 1 and 2, respectively), PF and preserved timolol (groups 3 and 4), and controls to vehicle of latanoprost or physiological buffered saline solution (groups 5 and 6). All subjects underwent LSCM of bulbar conjunctiva at baseline and 3 months after initiating therapy. The main outcomes were: mean density (MMD: cysts/mm(2)) and mean area (MMA: cysts/mm(2)) of epithelial microcysts. The relations between MMA and MMD with intraocular pressure (IOP), age, and mean defect (MD), were analyzed., Results: At baseline, microcysts were found in all subjects. At month three, MMD did not change in all groups (p > 0.05). MMA significantly increased only in group 1 from 2,158.81 ± 524.09 to 3,877.77 ± 867.31, and in group 2 from 2,019.71 ± 541.03 to 5,560.39 ± 1,176.14, with values significantly higher in group 2 (p < 0.001). Significant relations were not found between MMD and MMA with IOP, MD, and age (p > 0.05)., Conclusions: PGA increased MMA in therapy-naive glaucomatous patients, indicating a possible enhancement of the trans-conjunctival aqueous humor outflow. Therefore, conjunctiva seems an additional target tissue to evaluate the hydrodynamic pathways in glaucoma and modifications induced by medical therapy.

The purpose of this study is to assess the effect of palmitoylethanolamide (PEA) oral administration on intraocular pressure (IOP) and visual field damage progression in normal-tension glaucoma (NTG) patients. Thirty-two consecutive patients affected by NTG were enrolled and randomized in a 1:1 ratio to receive PEA treatment (group A) or no treatment (group B). Group A patients took ultramicronized 300 mg PEA tablets two times per day for six months. Best-corrected visual acuity (BCVA), IOP, and visual field test were evaluated at baseline and at the end of the six-month follow-up. No significant differences in clinical parameters between the two groups were observed at baseline. At six months, group A patients showed significant IOP reduction (from 14.4±3.2 mm Hg to 11.1±4.3 mm Hg, p<0.01). No statistically significant changes were seen in BCVA in either group. Visual field parameters significantly diminished in patients receiving PEA compared to baseline values (-7.65±6.55 dB vs. -4.55±5.31 dB, p<0.001; 5.21±4.08 dB vs. 3.81±3.02 dB, p<0.02; mean deviation [MD] and pattern standard deviation [PSD] respectively), while no significant changes were seen in group B. A generalized linear model demonstrated that the final IOP, MD, and PSD was affected only by the systemic PEA treatment (p<0.01 each) and not affected by demographic or clinical characteristic between the groups. Hence, systemic administration of PEA reduces IOP and improves visual field indices in individuals affected by NTG. Neither ocular nor systemic side effects were recorded during the study period.

Purpose: To investigate modifications with aging of the presence, distribution and morphologic features of conjunctiva-associated lymphoid tissue (CALT) in healthy human subjects using laser scanning in vivo confocal microscopy (IVCM)., Methods: A total of 108 (age range, 17-75 years) subjects were enrolled. In vivo confocal microscopy of the tarsal and bulbar conjunctiva, and impression cytology (IC) with CD3 (intra-epithelial T-lymphocytes) and CD20 (intra-epithelial B-lymphocytes) antibody immunofluorescence staining were performed. The main outcomes were subepithelial lymphocyte density (LyD), follicular density (FD), and follicular area (FA). The secondary outcomes were follicular reflectivity (FR), and lymphocyte density (FLyD), and CD3 and CD20 positivity., Results: Conjunctiva-associated lymphoid tissue was observed in all subjects (97% only superior and 3% in both superior and inferior tarsum). Lymphocyte density ranged from 7.8 to 165.8 cells/mm(2) (46.42 [18.37]; mean [SD]), FD from 0.5 to 19.4 follicles/mm(2) (5.3 [3.6]), and FA from 1110 to 96,280 mm(2) (26,440 [26,280]). All three parameters showed a highly significant inverse cubic relationship with age (P < 0.001); that is, in the first and last parameters a steep decline up to 35 years and above 65 years of age, with a plateau phase between these ages, whereas FA had a gradually decreasing rate of loss over the studied age range. CD3 and CD20 IC were consistent with these results., Conclusions: In vivo confocal microscopy was effective in revealing CALT and modifications these structures undergo with aging. Aging correlated with an involution of all parameters defining lymphoid structures. These modifications may account for the decrease of mucosal immune response and increase of ocular surface diseases in the elderly., (Copyright 2014 The Association for Research in Vision and Ophthalmology, Inc.)

Over the past decade, knowledge about the ocular surface in glaucoma has significantly increased through the use of in vivo laser scanning confocal microscopy (LSCM). This in vivo imaging method can show modifications at the cellular level induced by anti-glaucoma drugs on ocular surface structures and adnexa in the eye. High-quality images of the conjunctiva, cornea, limbus, meibomian glands, and lymphoid structures during therapy can be obtained. In addition, LSCM opened new fields of research on the patho-physiology of aqueous humor (AH) hydrodynamics in untreated, and in medically or surgically treated glaucomatous patients. In these conditions, an enhancement of the trans-scleral AH outflow contributed to clarification of the mechanism of action of different anti-glaucoma medications and surgical approaches. Finally, the use of LSCM represented a huge advance in evaluation of bleb functionality after filtration surgery, defining the hallmarks of AH filtration through the bleb-wall and distinguishing functional from nonfunctional blebs. Thus, signs seen with LSCM may anticipate clinical failure, guiding the clinician in planning the appropriate timing of the various steps in bleb management. In this review we summarize the current knowledge about in vivo LSCM of the ocular surface in glaucoma.

Purpose: The aim of this study is to investigate modifications in human cadaver corneas after different crosslinking procedures, including standard epi-off treatment, iontophoresis imbibition, and different exposure to ultraviolet A (UVA) sources (30 minutes at 3 mW and 9 minutes at 10 mW)., Methods: A total of 12 human cadaver corneas was examined and divided as follows: 3 served as control (group 1), 3 were treated with a standard epi-off procedure (group 2), 6 underwent iontophoresis imbibition for 5 minutes, and then 3 were irradiated for 30 minutes with 3 mW UVA (group 3), and 3 for 9 minutes at 10 mW UVA (group 4). Deformation amplitude index was measured before and after the corneas underwent treatment. After treatment, corneas were prepared for hematoxylin-eosin and immunohistochemistry evaluation. The expression of TUNEL, matrix metalloproteinase-1 (MMP-1), collagen type I, and CD34 was investigate in all samples., Results: The deformation amplitude index decreased in all groups, in particular in group 4, indicating an improvement of corneal biomechanical properties. Immunohistochemical staining showed a significant stromal alteration in group 2, mild damage in group 3, and no modifications in corneal morphology in group 4. The TUNEL (P < 0.001) and MMP-1 (P = 0.002) positivity was more evident in group 4. Collagen type I positivity significantly increased in groups 3 (P = 0.002) and 4 (P = 0.002). The CD34 expression was more evident in groups 2 (P = 0.003) and 3 (P = 0.003)., Conclusions: Iontophoresis imbibition followed by UVA irradiation for 9 minutes at 10 mW determined less tissue damage and better stromal remodeling.

Purpose: To determine differences in riboflavin concentration in the anterior, intermediate, and posterior stroma after 3 corneal cross-linking imbibition techniques (standard epithelial [epi]-off, epi-on, and iontophoresis-assisted administration) of 0.1% riboflavin., Design: Experimental laboratory investigation of human cadaver corneas not suitable for transplantation., Methods: Ten corneas underwent imbibition with epi-on (n = 3), epi-off (n = 3), iontophoresis (n = 3), and saline exposure (control; n = 1). Femtosecond laser was used to produce 3 8-mm discs of the superficial (0-150 μm), intermediate (150-300 μm), and deep stroma (>300 μm). Riboflavin concentration was measured with high-performance liquid chromatography. The main outcome measure was riboflavin concentration at the 3 evaluated depths., Results: The overall stromal concentration of riboflavin was 34.1 ± 7.1 μg/g in epi-off, 7.2 ± 3.7 μg/g in epi-on, and 15.0 ± 5.1 μg/g in iontophoresis. The mean riboflavin content in the superficial slice in the epi-off group was about 2-fold greater than that of the iontophoresis group (50.5 ± 5.3 μg/g and 23.6 ± 2.5 μg/g, respectively) and 4-fold greater than that of the epi-on group (11.7 ± 3.3 μg/g). Similar differences among the 3 groups were observed for the intermediate and posterior stromal slices, presenting an evident reduction of riboflavin concentration with increasing depth in all groups. Slice depth-dependent decrease in riboflavin concentration was statistically significant (general linear model (GLM); F1,6 = 62.265, P < .001), as was the group-dependent variation (GLM; F2,6 = 20.268, P = .002) and the slice depth group interaction (GLM; F2,6 = 18.004, P = .002)., Conclusions: Corneal cross-linking transepithelial iontophoresis imbibition yielded greater and deeper riboflavin saturation with respect to conventional epi-on, while maintaining the advantages of avoiding epithelial removal and shorter procedure time, but did not reach concentrations obtained with standard epi-off., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Purpose: To compare functional and morphological outcomes of femtosecond laser clear corneal incision (CCI) versus manual CCI during cataract surgery., Methods: Sixty eyes of 60 patients who underwent CCI during cataract surgery were randomized into two groups: femtosecond laser CCI (30 eyes) and manual CCI (30 eyes)., Results: There were no significant between-group differences in uncorrected distance visual acuity, corrected distance visual acuity, surgically induced astigmatism, and corneal aberrations. Keratometric astigmatism was significantly lower in the femtosecond laser CCI group compared to the manual CCI group at 30 and 180 days (P < .05). Central endothelial cell count was significantly higher in the femtosecond laser CCI group compared to the manual CCI group at 7 and 30 days postoperatively (P < .05). A lower increase of corneal thickness at the incision site was observed at 30 and 180 days postoperatively in the femtosecond laser CCI group compared to the manual CCI group (P < .05). In addition, femtosecond laser CCI showed a better morphology (lower percentage of endothelial and epithelial gaping and endothelial misalignment) compared to manual CCI at different time points. Total phacoemulsification time was significantly lower in the femtosecond laser CCI group (P < .05)., Conclusions: The femtosecond laser procedure was safe, efficient, and less damaging, as evidenced by lower central endothelial cell loss, lower increase of corneal thickness at the incision site, and better tunnel morphology compared to the manual technique.