Search

To reduce treatment burden and optimise patient outcomes in diabetic macular oedema, we present 1-year results from two phase 3 trials of faricimab, a novel angiopoietin-2 and vascular endothelial growth factor-A bispecific antibody.YOSEMITE and RHINE were randomised, double-masked, non-inferiority trials across 353 sites worldwide. Adults with vision loss due to centre-involving diabetic macular oedema were randomly assigned (1:1:1) to intravitreal faricimab 6·0 mg every 8 weeks, faricimab 6·0 mg per personalised treatment interval (PTI), or aflibercept 2·0 mg every 8 weeks up to week 100. PTI dosing intervals were extended, maintained, or reduced (every 4 weeks up to every 16 weeks) based on disease activity at active dosing visits. The primary endpoint was mean change in best-corrected visual acuity at 1 year, averaged over weeks 48, 52, and 56. Efficacy analyses included the intention-to-treat population (non-inferiority margin 4 Early Treatment Diabetic Retinopathy Study [ETDRS] letters); safety analyses included patients with at least one dose of study treatment. These trials are registered with ClinicalTrials.gov (YOSEMITE NCT03622580 and RHINE NCT03622593).3247 patients were screened for eligibility in YOSEMITE (n=1532) and RHINE (n=1715). After exclusions, 940 patients were enrolled into YOSEMITE between Sept 5, 2018, and Sept 19, 2019, and 951 patients were enrolled into RHINE between Oct 9, 2018, and Sept 20, 2019. These 1891 patients were randomly assigned to faricimab every 8 weeks (YOSEMITE n=315, RHINE n=317), faricimab PTI (n=313, n=319), or aflibercept every 8 weeks (n=312, n=315). Non-inferiority for the primary endpoint was achieved with faricimab every 8 weeks (adjusted mean vs aflibercept every 8 weeks in YOSEMITE 10·7 ETDRS letters [97·52% CI 9·4 to 12·0] vs 10·9 ETDRS letters [9·6 to 12·2], difference -0·2 ETDRS letters [-2·0 to 1·6]; RHINE 11·8 ETDRS letters [10·6 to 13·0] vs 10·3 ETDRS letters [9·1 to 11·4] letters, difference 1·5 ETDRS letters [-0·1 to 3·2]) and faricimab PTI (YOSEMITE 11·6 ETDRS letters [10·3 to 12·9], difference 0·7 ETDRS letters [-1·1 to 2·5]; RHINE 10·8 ETDRS letters [9·6 to 11·9], difference 0·5 ETDRS letters [-1·1 to 2·1]). Incidence of ocular adverse events was comparable between faricimab every 8 weeks (YOSEMITE n=98 [31%], RHINE n=137 [43%]), faricimab PTI (n=106 [34%], n=119 [37%]), and aflibercept every 8 weeks (n=102 [33%], n=113 [36%]).Robust vision gains and anatomical improvements with faricimab were achieved with adjustable dosing up to every 16 weeks, demonstrating the potential for faricimab to extend the durability of treatment for patients with diabetic macular oedema.F Hoffmann-La Roche.

IntroductionMicrovascular changes in eye and kidney shares some common factors in diabetes mellitus (DM). The purpose was to evaluate choroidal thickness (CT) and choriocapillaris (CC) density in patients with type 2 diabetes (T2D) and their association with diabetic kidney disease (DKD) using swept-source optical coherence tomography (SS-OCT).Research design and methodsA cross-sectional study was conducted with patients with T2D with mild or no diabetic retinopathy (DR) and non-diabetic controls. CT was measured with SS-OCT, and CC vascular density was measured with OCT angiography. These parameters were compared with inner retinal layers thickness in patients with and without DKD and non-diabetic controls.ResultsNinety-three eyes from patients with T2D and 34 eyes from controls volunteers were included. Within the T2D group, 56 eyes with DKD and 37 eyes from patients with no diabetic kidney disease were examined. A statistically significant reduction of CT was observed in patients with DKD compared with controls, with no difference in CC density. There was an association between ganglion cell layer and central choroidal thickness reduction in the DKD group.ConclusionsPatients with T2D with DKD showed a decrease in CT with no difference in CC density compared with non-diabetic controls. This thinning might be related to vascular changes of choroidal layers such as Haller’s and Sattler’s with preservation of CC density, which is crucial for outer retina and retinal pigment epithelium health. Longitudinal studies are warranted to determine the association of choroidal changes with the pathogenesis of diabetes, and its association with early DKD and progression to more severe DR.

Peripheral T-cell lymphomas (PTCLs) are a heterogeneous group of aggressive neoplasms. The involvement of ocular structures in haematological neoplasms is rare and usually associated with central nervous system involvement, which may occur as a result of orbital invasion and optic nerve infiltration. In this case report, we describe ocular findings using the novel swept source optical coherence tomography (SS-OCT) in a case of aggressive T-cell lymphoma. SS-OCT has faster scanning speed, deeper tissue penetration due to its longer wavelength laser of 1050 nm and wider scanning areas. In the present case, SS-OCT was helpful in documenting increased retinal nerve fibre layer thickness and prelaminar protrusion associated with visual loss in a patient with an aggressive T-cell lymphoma.

Purpose To evaluate differences in the thickness of the individual macular layers between early, moderate, and severe glaucomatous eyes and compare them with healthy controls. Patients and methods Subjects with glaucoma presenting typical optic nerve head findings, high intraocular pressure with or without visual field (VF) damage and normal controls were included. All participants underwent 24-2 perimetry and spectral-domain OCT. Patients were divided into three groups (early, moderate, and severe) based on the mean deviation of the VF and a healthy control group. The device segmented the layers automatically, and their measurements were plotted using the means of the sectors of the inner (3mm) and outer (6mm) circles of the ETDRS grid. Results A total of 109 eyes qualified for the study: 14 in the control group and 52, 18 and 25 in the early, moderate and severe groups, respectively. Mean age was 66.13 (SD=12.38). The mean thickness of the circumpapillary retinal nerve fiber layer (RNFL), total macular thickness (TMT), macular RNFL, ganglion cell layer (GCL) and inner plexiform layer (IPL) were significantly different between the 4 groups, with progressive decrease in thickness. Significant overall difference was found for the inner nuclear layer (INL), and the severe glaucoma group presented thicker measurements than controls and early glaucoma. Outer nuclear layer (ONL) was thinner in severe glaucoma group compared with early glaucoma group. Conclusion Individual macular layer measurement using the inner and outer circles of the ETDRS grid is useful to evaluate different stages of glaucoma. The INL thickening and ONL thinning in advanced glaucoma should be explored in the future studies.

Spinocerebellar ataxia type 7 (SCA7) is a polyglutamine disease that progressively affects the cerebellum, brainstem, and retina. SCA7 is quite rare, and insights into biomarkers and pre-clinical phases are still missing. We aimed to describe neurologic and ophthalmological findings observed in symptomatic and pre-symptomatic SCA7 subjects. Several neurologic scales, visual acuity, visual fields obtained by computer perimetry, and macular thickness in optical coherence tomography (mOCT) were measured in symptomatic carriers and at risk relatives. Molecular analysis of the ATXN7 was done blindly in individuals at risk. Thirteen symptomatic carriers, 3 pre-symptomatic subjects, and 5 related controls were enrolled. Symptomatic carriers presented scores significantly different from those of controls in most neurologic and ophthalmological scores. Gradual changes from controls to pre-symptomatic and then to symptomatic carriers were seen in mean (SD) of visual fields - 1.34 (1.15), - 2.81 (1.66). and - 9.56 (7.26); mOCT - 1.11 (2.6), - 3.48 (3.54), and - 7.73 (2.56) Z scores; and "Spinocerebellar Ataxia Functional Index (SCAFI)" - 1.16 (0.28), 0.65 (0.56), and - 0.61 (0.44), respectively. Visual fields and SCAFI were significantly correlated with time to disease onset (pre-symptomatic)/disease duration (symptomatic carriers). Visual fields, mOCT, and SCAFI stood out as candidates for state biomarkers for SCA7 since pre-symptomatic stages of disease.

PURPOSE Macular telangiectasia (MacTel) Type 2 is a progressing neurovascular disease of the macula, currently lacking effective treatment. This study assessed the effect of nondamaging retinal laser therapy (NRT) compared with sham. METHODS Twelve MacTel patients were enrolled in this double-masked, controlled, randomized clinical trial. For the nine patients with both eyes eligible, one eye was randomized to NRT or sham and the other received alternate treatment. For three patients with only one eye eligible, that eye was randomly assigned either NRT or sham. Ellipsoid zone disruption, best-corrected visual acuity, and macular automated perimetry at 12 months served as structural and functional measures. RESULTS Eleven eyes were randomized to sham and 10 to NRT. Baseline best-corrected visual acuity was 66 letters (20/50) for sham and 72 letters (20/40) for NRT (P = 0.245). Ellipsoid zone disruption area was 298 µm2 in sham and 368 µm2 in NRT (P = 0.391). At 12 months, ellipsoid zone disruption increased by 24% in sham and decreased by 34% in NRT (P < 0.001). Best-corrected visual acuity measures remained stable during follow-up compared with baseline. At 1 year, the mean macular sensitivity was 28 dB in the NRT group, compared with 26 dB in sham. CONCLUSION Nondamaging retinal laser therapy was safe and well tolerated in patients with MacTel and resulted in structural and functional improvements, which could represent a protective effect of laser-induced hyperthermia. Longer follow-up and larger number of patients should help corroborate these effects.

ObjectiveThis study aimed to establish the utility values of different health states associated with diabetic retinopathy in a Brazilian sample to provide input to model-based economic evaluations.Subjects and methodsThis cross-sectional study was performed in a sample of patients with type 2 diabetes mellitus (T2D) who underwent teleophthalmology screening at a primary care service from 2014 to 2016. Five diabetic retinopathy health states were defined: absent, non-sight-threatening, sight-threatening, and bilateral blindness. Utility values were estimated using the Brazilian EuroQol five dimensions (EQ-5D) tariffs. Descriptive statistics were calculated. Analysis of covariance was performed to adjust the utility values for potential confounders.ResultsThe study included 206 patients. The mean (± standard deviation [SD]) utility value was 0.765 ± 0.19 (95% confidence interval [CI], 0.740–0.790). The adjusted mean utility value was 0.748 (95% CI, 0.698–0.798) in patients without diabetic retinopathy, 0.752 (95% CI, 0.679–0.825) in those with non-sight-threatening state, 0.628 (95% CI, 0.521–0.736) in those with sight-threatening state, and 0.355 (95% CI, 0.105–0.606) in those with bilateral blindness. A significant utility decrement was found between patients without diabetic retinopathy and those with a sight-threatening health state (0.748 vs. 0.628, respectively, p = 0.04).ConclusionsThe findings suggest that a later diabetic retinopathy health state is associated with a decrement in utility value compared with the absence of retinopathy in patients with T2D. The results may be useful as preliminary input to model-based economic evaluations. Further research is needed to investigate the impact of diabetic retinopathy on health-related quality of life in a sample more representative of the Brazilian population.

Purpose To evaluate differences in the thickness of the individual macular layers between early, moderate, and severe glaucomatous eyes and compare them with healthy controls. Patients and Methods Subjects with glaucoma presenting typical optic nerve head findings, high intraocular pressure with or without visual field (VF) damage and normal controls were included. All participants underwent 24–2 perimetry and spectral-domain OCT. Patients were divided into three groups (early, moderate, and severe) based on the mean deviation of the VF and a healthy control group. The device segmented the layers automatically, and their measurements were plotted using the means of the sectors of the inner (3mm) and outer (6mm) circles of the ETDRS grid. Results A total of 109 eyes qualified for the study: 14 in the control group and 52, 18 and 25 in the early, moderate and severe groups, respectively. Mean age was 66.13 (SD=12.38). The mean thickness of the circumpapillary retinal nerve fiber layer (RNFL), total macular thickness (TMT), macular RNFL, ganglion cell layer (GCL) and inner plexiform layer (IPL) were significantly different between the 4 groups, with progressive decrease in thickness. Significant overall difference was found for the inner nuclear layer (INL), and the severe glaucoma group presented thicker measurements than controls and early glaucoma. Outer nuclear layer (ONL) was thinner in severe glaucoma group compared with early glaucoma group. Conclusion Individual macular layer measurement using the inner and outer circles of the ETDRS grid is useful to evaluate different stages of glaucoma. The INL thickening and ONL thinning in advanced glaucoma should be explored in the future studies.

A injeção intravítrea é o procedimento oftalmológico mais realizado no mundo. Através dessa técnica é possível administrar medicamentos para o segmento posterior do olho, sendo a via de escolha para o tratamento da maioria das patologias coriorretinianas. O evento ocular adverso mais grave é a endoftalmite pós injeção. Diversas medidas foram sugeridas para diminuição do risco dessa complicação, com evidências variáveis. Tendo em vista o grande número de injeções realizado em nosso serviço de oftalmologia do Hospital de Clínicas de Porto Alegre (HCPA), realizamos uma revisão da literatura com o objetivo de definir as melhores práticas. Nós descrevemos a evidência disponível para os principais aspectos dos diferentes estágios do procedimento (pré injeção, peri injeção e pós injeção) e apresentamos nosso protocolo. A medida com maior evidência científica na profilaxia da endoftalmite é a aplicação de iodopovidona tópica pelo menos trinta segundos antes da injeção. Intravitreal injection is the most widely performed ophthalmologic procedure in the world. This technique allows for delivering therapeutic substances to the posterior segment of the eye, being the route of choice for the treatment of most chorioretinal diseases. The most feared adverse event is post-injection endophthalmitis. Many measures have been described to lower the risk of this complication, with variable evidence. In view of the great number of injections performed at our ophthalmology practice at Hospital de Clínicas de Porto Alegre (HCPA), we searched the literature for available evidence on the best practice standards. We describe the available evidence for major aspects of the different stages of the procedure (pre-injection, peri-injection, and post-injection) and then introduce our protocol. The measure with most scientific evidence of efficacy in preventing endophthalmitis is topical povidoneiodine administration at least 30 seconds before the injection.

To compare choroidal thickness (CT) measurements in preeclamptic and healthy women in the third trimester of pregnancy using optical coherence tomography. This cross-sectional study included 148 eyes of 74 women, divided into two groups: 27 healthy pregnant women in the third trimester (control group) and 47 age-matched pregnant women in the third trimester with preeclampsia (PE group). Of the 47 subjects in preeclampsia group, 26 were classified as having mild PE and 21 as having severe PE. Choroidal thickness was measured at ten different locations: at the fovea and every 500 µm from the fovea up to 2500 µm temporally and up to 2000 µm nasally. Comparing CT of both groups, choroid always tended to be thicker in subjects with preeclampsia in comparison with healthy pregnant women, with statistical significance in nasal measures. Dividing PE group according to disease severity, women with severe preeclampsia tended to have thicker choroids in comparison with mild preeclamptic and healthy pregnant women. Choroid was also significantly thicker in preeclamptic patients with serous retinal detachment (SRD) in comparison with preeclamptic patients without SRD (P

MicroRNAs (miRNAs/miRs) are involved in the pathogenesis of diabetes mellitus and its chronic complications, and their circulating levels have emerged as potential biomarkers for the development and progression of diabetes. However, few studies have examined the expression of miRNAs in diabetic retinopathy (DR) in humans. This case‐control study aimed to investigate whether the plasma levels of miR‐29b and miR‐200b are associated with DR in 186 South Brazilians with type 2 diabetes (91 without DR, 46 with non‐proliferative DR and 49 with proliferative DR). We also included 20 healthy blood donors to determine the miRNA expression in the general population. Plasma levels of miR‐29b and miR‐200b were quantified by reverse transcription‐quantitative polymerase chain reaction (RT‐qPCR). Proliferative DR was inversely associated with plasma levels of miR‐29b (unadjusted OR = 0.694, 95% CI: 0.535‐0.900, P = 0.006) and miR‐200b (unadjusted OR = 0.797, 95% CI: 0.637‐0.997, P = 0.047). However, these associations were lost after controlling for demographic and clinical covariates. In addition, patients with type 2 diabetes had lower miR‐200b levels than blood donors. Our findings reinforce the importance of addressing the role of circulating miRNAs, including miR‐29 and miR‐200b, in DR.

BACKGROUND AND OBJECTIVE: To evaluate retinal layer changes in patients with type 2 diabetes, microalbuminuria, and no diabetic retinopathy, and to investigate its possible relationship with age, gender, diabetes duration, urinary albumin excretion (UAE), glycosylated hemoglobin, and hypertension. PATIENTS AND METHODS: A prospective, cross-sectional study was performed in 60 patients divided into three groups: diabetic patients with normal UAE, diabetic patients with microalbuminuria, and controls. Retinal thickness was evaluated by Early Treatment Diabetic Retinopathy Study grid using spectral-domain optical coherence tomography. RESULTS: The average and sectoral macular thicknesses of the ganglion cell layer (GCL) were significantly thinner in the microalbuminuria group compared to normal UAE group and controls ( P < .005). UAE was the only factor related to this reduction in a multiple linear regression analysis. CONCLUSIONS: The GCL thickness was reduced in eyes in patients with type 2 diabetes and microalbuminuria before clinical signs of diabetic retinopathy. Inner retinal neurodegeneration was independently associated with albuminuria. [ Ophthalmic Surg Lasers Imaging Retina . 2018;49:e36–e43.]

Lucas Brandolt Farias,1,2 Daniel Lavinsky,1,2 Camila Zanella Benfica,1,2 Monica Oliveira da Silva,1,2 Jacó Lavisnky,1,2 Luis Henrique Canani2,3 1Department of Ophthalmology, Federal University of Rio Grande do Sul, Porto Alegre, Brazil; 2Ophthalmology Section, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil; 3Department of Endocrinology, Federal University of Rio Grande do Sul, Porto Alegre, Brazil Purpose: To evaluate choroidal thickness and volume in patients with type 2 diabetes and microalbuminuria using spectral-domain optical coherence tomography. Methods: We recruited 37 diabetic patients without diabetic retinopathy (18 normoalbuminuric and 19 microalbuminuric) and 21 healthy controls. Choroidal thickness and volume were mapped using the automated Early Treatment Diabetic Retinopathy Study grid and a topographic map of thickness was generated manually. Choroid was also measured at 10 locations under the fovea, temporally and nasally. Results: Mean choroidal thickness and volume among patients with diabetes and microalbuminuria was reduced in all locations compared to controls (P

Pregnancy is an independent risk factor for the progression of diabetic retinopathy (DR). A possible relation with morphological changes of the choroid should be studied. The aim of this study was to analyze choroidal thickness measurements of nondiabetic pregnant women and of pregnant women with type 1, type 2 and gestational diabetes mellitus using spectral-domain optical coherence tomography (OCT). This cross-sectional study included 144 eyes of 72 pregnant women in the third trimester divided into four groups: Group 1 consisted of 27 nondiabetic pregnant women (control group); Group 2 consisted of 15 pregnant women with gestational diabetes mellitus (GDM); Group 3 consisted of 16 pregnant women with type 2 diabetes mellitus (T2DM); and Group 4 consisted of 14 pregnant women with type 1 diabetes mellitus (T1DM). Choroidal thickness was measured using EDI-OCT at ten different locations: at the fovea and every 500µm from the fovea up to 2500µm temporally and up to 2000µm nasally. Other variables such as gestational age, glycosylated hemoglobin values (HbA1c), time from DM diagnosis, hypertension and severity of DR were analyzed. The analysis of the 4 groups adjusted for the presence of hypertension showed a thinner choroid in patients with T1DM in all locations, with statistical significance in subfoveal and temporal measurements. In the comparison only between patients with DM, adjusted for HbA1c, time from diagnosis and presence of hypertension and DR, choroid of patients with T1DM remained thinner at all macular points. In conclusion, our study showed no statistically difference in choroidal thickness between nondiabetic pregnant women, pregnant women with GDM and pregnant women with T2DM during the third trimester. On the other hand, pregnant women with T1DM had significantly thinner choroidal thickness measurements. Disclosure C.Z. Benfica: None. T. Zanella: None. L.B. Farias: None. M.R. Oppermann: None. L.H.S. Canani: None. D. Lavinsky: None.

Objective: This study assessed microvascular complications (MC) occurrence in renal posttransplant diabetes mellitus (PTDM). Methods: Patients ≥ 5 years of PTDM were included from a cohort of 895 kidney recipients (KR) transplanted in 2000-2011. Diabetic retinopathy (DR) was evaluated by fundus photographs (FP) and optical coherence tomography (OCT). Diabetes kidney disease was evaluated by protein to creatinine ratio (PCR) and eGFR. Distal polyneuropathy (DPN) was assessed by Michigan Protocol/monofilament foot exam. Ewing protocol identified cardiovascular autonomic neuropathy (CAN). Controls were KR transplanted in the same period but without PTDM (NPTDM). Results: After 578 weeks, 135 (15%) KR developed PTDM, 64 with PTDM ≥ 5 years. None of PTDM KR presented DR at FP but thinning of inner retinal layers was observed with OCT (Figure 1). More than 60% of PTDM KR had DPN (OR 1.55; CI 1.26-1.91; p Conclusions: This is the first longitudinal study to assess MC in PTDM KR. A lower than expected prevalence as well as a different clinical course of the MC was observed. PTDM seems to be a unique type of DM and its consequences may be milder than expected in type 1 and type 2 DM. Disclosure T.M. Londero Gai: None. L.S. Giaretta: None. R.C. Manfro: None. L.H. Canani: None. D. Lavinsky: None. C.B. Leitao: None. A. Bauer: None.

Camila Zanella Benfica,1,2 Teresinha Zanella,3 Lucas Brandolt Farias,1,2 Maria Lúcia Rocha Oppermann,1,3 Luis Henrique Santos Canani,1,4 Daniel Lavinsky1,2 1Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, Brazil; 2Department of Ophthalmology, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil; 3Department of Gynecology and Obstetrics, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil; 4Department of Endocrinology, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil Purpose: To analyze choroidal thickness (CT) of pregnant women with type 1 diabetes mellitus (DM), type 2 DM and gestational diabetes mellitus (GDM) using spectral-domain optical coherence tomography. Patients and methods: This cross-sectional study included 144 eyes of 72 pregnant women in the third trimester divided into four groups: 27 non-diabetic pregnant women; 15 pregnant women with GDM; 16 with type 2 DM and 14 with type 1 DM. CT was measured using optical coherence tomography at ten different locations. We also analyzed possible confounding factors, such as gestational age, glycosylated hemoglobin, time from DM diagnosis, hypertension and severity of diabetic retinopathy. Results: The comparison between the four groups showed a thinner choroid in patients with type 1 DM in all locations, with statistical significance in subfoveal and temporal measurements. When comparing only patients with type 1 and type 2 DM, adjusting for confounding factors, the choroid of patients with type 1 DM remained thinner at all macular points, also with statistical significance in subfoveal and temporal measurements. Conclusion: Pregnant women with type 1 DM had significantly thinner CT measurements on subfoveal and temporal locations. No differences were found in CT between the control group and pregnant women with GDM and type 2 DM. Keywords: choroid, enhanced depth imaging optical coherence tomography, pregnancy, gestational diabetes mellitus, diabetes mellitus

Background The impact of pregnancy on the choroid is still under investigation. The aim of this study is to compare choroidal thickness measurements of healthy pregnant women in the third trimester and healthy non-pregnant women using spectral-domain optical coherence tomography (OCT). Methods This cross-sectional study included 122 eyes of 61 women, divided into two groups: 27 healthy pregnant women in the third trimester and 34 age-matched healthy non-pregnant women. Choroidal thickness was measured using Enhanced Depth Imaging OCT at ten different locations: at the fovea and every 500 µm from the fovea up to 2500 µm temporally and up to 2000 µm nasally. Results There were no significant differences in the ten measurements of choroidal thickness comparing both groups. Mean subfoveal choroidal thickness was 304.1 + 9.6 µm in the control group and 318.1 + 15.6 µm in the pregnant women group (p = 0.446). There was also no statistically significant association between gestational age and choroidal thickness measurements in the healthy pregnant women group. Conclusions Our study showed no statistically difference in choroidal thickness between healthy non-pregnant women and healthy pregnant women in the third trimester.

To investigate the relationship between retinal sensitivity and persistence of subretinal fluid and then to analyze microperimetry as a prognostic predictor of acute central serous chorioretinopathy.A prospective observational study. Fourteen eyes of 14 patients presenting with first episode acute central serous chorioretinopathy were enrolled and underwent ocular examination, spectral domain optical coherence tomography, and MAIA microperimetry were performed. After three months of follow-up, without any treatment, visual acuity and spectral domain optical coherence tomography macular thickness assessments and microperimetry were repeated. The main outcome was to find a relation between initial macular sensitivity and persistence of subretinal fluid. A receiver operating characteristic curve was plotted to indicate the best macular sensitivity cutoff point that would be able to predict whether a patient with acute central serous chorioretinopathy would progress to the chronic form. According to the cutoff, we calculated the sensitivity, specificity, and positive and negative predictive values for macular sensitivity as a method to predict persistence of subretinal fluid.On the basis of the receiver operating characteristic curve, a cutoff of 20 dB macular sensitivity was obtained, as the best balance between sensitivity and specificity to predict chronicity. Using this cutoff, the method had a sensitivity of 71% and specificity of 100% with a positive predictive value of 100% and negative predictive value of 78%. Furthermore, it was found that eyes with acute central serous chorioretinopathy and microperimetry of less than 20 dB had a relative risk of 4.5 to develop subretinal fluid persistence.Microperimetry with a cutoff of 20 dB may be a useful test to predict the persistence of subretinal fluid, allowing the ophthalmologist to use treatment tools earlier, preventing extracellular damage and visual impairment.

PURPOSE Laser therapy for diabetic macular edema and other retinal diseases has been used within a wide range of laser settings: from intense burns to nondamaging exposures. However, there has been no algorithm for laser dosimetry that could determine laser parameters yielding a predictable extent of tissue damage. This multimodal imaging and structural correlation study aimed to verify and calibrate a computational model-based titration algorithm for predictable laser dosimetry ranging from nondamaging to intense coagulative tissue effects. METHODS Endpoint Management, an algorithm based on a computational model of retinal photothermal damage, was used to set laser parameters for various levels of tissue effect. The algorithm adjusts both power and pulse duration to vary the expected level of thermal damage at different percentages of a reference titration energy dose. Experimental verification was conducted in Dutch Belted rabbits using a PASCAL Streamline 577 laser system. Titration was performed by adjusting laser power to produce a barely visible lesion at 20 ms pulse duration, which is defined as the nominal (100%) energy level. Tissue effects were then determined for energy levels of 170, 120, 100, 75, 50, and 30% of the nominal energy at 1 hour and 3, 7, 30, and 60 days after treatment. In vivo imaging included fundus autofluorescence, fluorescein angiography, and spectral-domain optical coherence tomography. Morphologic changes in tissue were analyzed using light microscopy, as well as scanning and transmission electron microscopy. RESULTS One hundred and seventy percent and 120% levels corresponded to moderate and light burns, respectively, with damage to retinal pigment epithelium, photoreceptors, and at highest settings, to the inner retina. 50% to 75% lesions were typically subvisible ophthalmoscopically but detectable with fluorescein angiography and optical coherence tomography. Histology in these lesions demonstrated some selective damage to retinal pigment epithelium and photoreceptors. The 30% to 50% lesions were invisible with in vivo multimodal imaging, and damage was limited primarily to retinal pigment epithelium, visible best with scanning electron microscopy. Over time, photoreceptors shifted into the coagulated zone, reestablishing normal retinal anatomy in lesions ≤100%, as seen in optical coherence tomography and light microscopy. Transmission electron microscopy at 2 months demonstrated restoration of synapses between shifted-in photoreceptors and bipolar cells in these lesions. Retinal pigment epithelium monolayer restored its continuity after 1 week in all lesions. No damage could be seen

PURPOSE: To evaluate the effect of intravitreal triamcinolone acetonide (TA) on healing of retinal photocoagulation lesions using drug and laser dosing typically employed in clinical practice. METHODS: Laser burns with a 267-μm retinal beam size at 532-nm wavelength were applied to 40 eyes of Dutch belted rabbits. Barely visible to intense lesions were produced with pulses of 5, 10, 20, and 50 milliseconds and power of 175 mW. Eyes received intravitreal injections of either 2 mg TA/50 μL or balanced salt solution administered either 1 week before or immediately after laser treatment. Lesion grades were assessed acutely ophthalmoscopically and by a masked observer histologically at 1, 3, 7, 30, and 60 days. RESULTS: Both TA groups demonstrated significant reduction in retinal thickness throughout follow-up compared with balanced salt solution groups (P < 0.001). The width of the lesions at 1 day after injection was not significantly different between groups. However, by 7 days, the lesions in balanced salt solution groups contracted much more than in the TA groups, especially the more intense burns, and this difference persisted to 2 months. The healing rate of the barely visible burns was not significantly affected by TA compared with the balanced salt solution control eyes. CONCLUSION: Triamcinolone acetonide injection previously or concurrently with photocoagulation significantly decreases laser-induced edema but interferes with lesions healing, thereby leaving wider residual scarring, especially persistent in more intense burns.

Technologies for multimodal digital imaging of vitreoretinal diseases have improved the accuracy of diagnosis and the depth of the knowledge of the mechanisms of disease and their response to treatments. Optic coherence tomography (OCT) has become a mandatory tool for the management and for the follow-up of retinal pathologies. OCT technology evolved in the last two decades from time-domain to spectral domain and recently to the swept-source OCTs (SS-OCT). SS-OCT improved the depth of imaging and the scan speed, thus adding novel algorithms and features such as for vitreous and vitreoretinal interface evaluation, choroid segmentation and mapping, OCT angiography and En-face OCT. The multimodal approach using SS-OCT is expected to advance the understanding of retinal pathologies such as age related macular degeneration, diabetic maculopathy, central serous chorioretinopathy, the pachychoroid spectrum and macular telangiectasia. Surgical vitreoretinal diseases such as vitreo-macular traction syndrome, epiretinal membrane, retinal detachment, proliferative vitreoretinal retinopathy and diabetic traction retinal detachment also will be better understood and documented with SS-OCT. This technology also provides great utility for a broad spectrum of ophthalmic pathologies including glaucoma, uveitis, tumors and anterior segment evaluation.

To describe the morphologic characteristics of commotio retinae using spectral-domain optical coherence tomography and to evaluate its utility in prognosis and follow-up.Consecutive patients with commotio retinae underwent complete ophthalmic examination, color fundus photography, spectral-domain optical coherence tomography, fundus autofluorescence, and near-infrared autofluorescence.There were 11 eyes of 11 patients (8 men), with a mean age of 30.8 ± 12.1 years. The follow-up ranged from 9 days to 6 months. Spectral-domain optical coherence tomography identified hyperreflectivity underneath the inner/outer segment junction in the area of commotio retinae in 9 patients (81.1%), which subsided in a few days. Five patients (45.5%) revealed areas of disruption of the inner/outer segment junction and hyperreflectivity of the overlying retina, which progressed to external retinal atrophy and visual loss (P = 0.002). The 5 patients with visual sequelae revealed pigment disorders and alterations in fundus autofluorescence and near-infrared autofluorescence during follow-up, and 3 patients (60%) presented with intraretinal hemorrhages.Spectral-domain optical coherence tomography of mild lesions with good visual outcome showed transient hyperreflectivity of the outer retina. The cases with severe trauma were related to acute disruption of the inner/outer segment junction and hyperreflectivity of the overlying retina and were regularly associated with retinal atrophy, pigment disturbance, and poor visual prognosis.

BACKGROUND Sympathetic ophthalmia is a rare, bilateral, diffuse granulomatous uveitis that usually occurs after open globe injury or intraocular surgery. To our knowledge, findings of this condition using spectral-domain optical coherence tomography have not been previously described. METHODS Case report. RESULTS A case of sympathetic uveitis after a tectonic corneal-scleral keratoplasty because of a fungal keratitis is reported. Spectral-domain optical coherence tomographic images revealed a multilobular serous retinal detachment in the sympathizing eye. The subretinal space was divided by thin septa into compartments filled with subretinal fluid and some high reflective compounds. CONCLUSION Spectral-domain optical coherence tomographic imaging noninvasively demonstrated a multilobular serous retinal detachment in the sympathizing eye, sharing the same features previously reported in patients with Vogt-Koyanagi-Harada syndrome.

Purpose Shorter pulses used in pattern scanning photocoagulation (10-20 milliseconds [ms]) tend to produce lighter and smaller lesions than the Early Treatment Diabetic Retinopathy Study standard 100-ms exposures. Smaller lesions result in fewer complications but may potentially reduce clinical efficacy. It is worthwhile to reevaluate existing standards for the number and size of lesions needed. Methods The width of the coagulated zone in patients undergoing retinal photocoagulation was measured using optical coherence tomography. Lesions of "moderate," "light," and "barely visible" clinical grades were compared for 100, 200, and 400 μm spot sizes and pulse durations of 20 ms and 100 ms. Results To maintain the same total area as in 1,000 standard burns (100 ms, moderate) with a 400-μm beam, a larger number of 20-ms lesions are required: 1,464, 1,979, and 3,520 for moderate, light, and barely visible grades, respectively. Because of stronger relative effect of heat diffusion with a smaller beam, with 200 μm this ratio increases: 1,932, 2,783, and 5,017 lesions of 20 ms with moderate, light, and barely visible grades correspond to the area of 1,000 standard burns. Conclusion A simple formula is derived for calculation of the required spot spacing in the laser pattern for panretinal photocoagulation with various laser parameters to maintain the same total coagulated area.

The use of topical agents poses unique and challenging hurdles for drug delivery. Topical steroids effectively control ocular inflammation, but are associated with the well-recognized dilemma of patient compliance. Although administration of topical antimicrobials as prophylaxis is acceptable among ophthalmologists, this common practice has no sound evidence base. Developing a new antimicrobial agent or delivery strategy with enhanced penetration by considering the anatomical and physiological constraints exerted by the barriers of the eye is not a commonly perceived strategy. Exploiting the permeability of the sclera, subconjunctival routes may offer a promising alternative for enhanced drug delivery and tissue targeting.Ocular drug delivery strategies were reviewed for ocular inflammation and infections clinically adopted for newer class of antimicrobials, which use a multipronged approach to limit risks of endophthalmitis.The analysis substantiates a new transscleral drug delivery therapeutic approach for cataract surgery.A new anti-inflammatory and anti-infective paradigm that frees the patient from the nuisance of topical therapeutics is introduced, opening a large investigative avenue for future improved therapies.

PURPOSE The purpose of this study was to describe clinical, angiographic, and tomo-graphic prognostic factors in central serous chorioretinopathy. METHODS This is a prospective uncontrolled case series. Forty-six eyes (43 patients) with clinical and angiographic findings consistent with central serous chorioretinopathy were included. Clinical data regarding age, sex, duration of symptoms, associated conditions, and best-corrected visual acuity (BCVA) were collected at baseline. Optical coherence tomography was performed at baseline, monthly until fluid resolution occurred, and at the end of the follow-up. RESULTS Mean follow-up was 22.8 months. Mean baseline and final logarithm of the minimum angle of resolution BCVA were 0.3 and 0.12 (P < 0.0001), respectively. Statistically significant correlations were observed between the baseline BCVA as well as duration of symptoms and final BCVA. Angiographic patterns were not significantly correlated with the visual outcome. Shorter periods of subfoveal fluid during the follow-up were correlated with better visual acuity. Mean foveal thickness after fluid resolution was 178 +/- 22 microm. Both baseline and final BCVA were strongly correlated with the foveal thickness after fluid resolution. CONCLUSION Initial BCVA may be a reliable predictor of the visual outcome in central serous chorioretinopathy. Eyes with worse BCVA may have an increased risk of foveal atrophy. Fluid persistence on optical coherence tomography may be associated with worse visual prognosis.

Neonatal cerebral hypoxia-ischemia (HI) is an important cause of neurological deficits. The Levine-Rice model of unilateral HI is a useful experimental tool, but the resulting brain damage is mainly restricted to one hemisphere. Since the rat presents morphological and biochemical asymmetries between brain hemispheres, behavioral outcome from this model is probably dependent on which hemisphere is damaged. We here investigated the effects of sex and lesioned hemisphere on the outcome of open field, plus maze, inhibitory avoidance and water maze tasks in adult rats previously submitted to neonatal unilateral HI. Females were more active than males in some of studied parameters and males presented better spatial learning. Hypoxia-ischemia caused spatial deficits independently of sex or damaged hemisphere. Right-HI increased locomotion only in males and caused working memory in females and on aversive learning in both males and females. Morphological analysis showed that right-HI animals presented greater reduction of ipsilateral striatum area, with females being more affected. Interestingly, males showed greater hippocampal volume. These results show that task performance and cerebral damage extension are lateralized and sex-dependent, and that the right hemisphere, irrespective of sex, is more vulnerable to neonatal cerebral hypoxia-ischemia.

Made available in DSpace on 2020-12-10T20:12:33Z (GMT). No. of bitstreams: 0 Previous issue date: 2008-02-01 Background: This in vivo study assessed and compared the effectiveness of an aqueous indocyanine green (ICG) formulation (R-ICG) and a lipid ICG formulation (L-ICG) in occluding the rabbit choriocapillaris, and determined the singlet oxygen quantum yields and aggregation properties of both formulations in vitro. Methods: Singlet oxygen production and aggregation were compared. The eye fundus of 30 albino rabbits was irradiated 0-15 min after dye injection using an 810 nm diode laser. Fluorescein angiography and light microscopy were used to evaluate the safety and efficacy of R-ICG and L-ICG. Results: L-ICG decreased the dimerisation constant and the tendency of ICG to form aggregates, and increased the efficiency of ICG in generating singlet oxygen (R-ICG, Phi Delta= 0.120 and L-ICG, Phi Delta= 0.210). Using a 10 mg/kg dose, choriocapillaris occlusion was achieved at a light dose of 35.8 J/cm(2) with L-ICG and 71.6 J/cm(2) with R-ICG with minimal damage to the neurosensory retina. Conclusion: Restrictions to the use of ICG in aqueous solution, low singlet oxygen quantum yields and high aggregation tendency, were overcome with L-ICG. The lower laser irradiance required to obtain choriocapillaris occlusion may suggest that L-ICG is a more potent and selective photosensitiser than R-ICG. Hosp Olhos Araraquara, Retinal Diagnost & Treatment Div, BR-14802530 Araraquara, SP, Brazil Univ Fed Sao Paulo, Paulista Sch Med, Dept Ophthalmol, Sao Paulo, Brazil State Univ Sao Paulo USP Ribeirao Preto, Dept Chem, Riberir Preto, Brazil Univ Calif Irvine, Dept Ophthalmol, Irvine, CA USA State Univ Sao Paulo USP Ribeirao Preto, Dept Chem, Riberir Preto, Brazil

Ocular ischemic syndrome is a devastating eye disease caused by severe carotid artery stenosis. The reduction of blood flow produced by bilateral common carotid artery occlusion (BCCAO) of rats for 7 days induces events related to gliosis with no evident histological damage. However, retinal degeneration and cellular death occur after 90 days of BCCAO. Our purpose has been to investigate the effects of BCCAO for 30 days in the retina of adult rats. Adult Wistar rats were submitted to BCCAO or sham surgery. Both direct and consensual pupillary light reflexes were investigated before and after surgery, everyday for the first week and weekly for 30 days. After 1 month, eyes were enucleated and embedded in paraffin. The retinal ganglion cell (RGC) density and thickness of the internal plexiform (IPL), internal nuclear, outer plexiform, and outer nuclear layers were estimated. Four rats of the BCCAO group (50%) lost the direct pupillary reflex in both eyes, three rats (37%) lost this reflex in one eye, and only one (13%) maintained it in both eyes. RGC density (cells/mm) was diminished in the BCCAO group, and a significant decrease was found in the total retina and IPL thickness; however, no changes were evident in the other layers. BCCAO pupillary-reflex-negative rats presented with a significant decrease in total retinal thickness and retinal ganglion cell density compared with the sham group. Both BCCAO pupillary-reflex-positive) and -negative rats showed a decrease in IPL compared with the sham group. This study demonstrates that BCCAO for 30 days induces functional and morphological damage to the retina with loss of the pupillary reflex and a decrease in IPL thickness and RGC number. We suggest that this protocol might be used as a model for ocular ischemic syndrome in the rat.

Agmatine is a new putative neurotransmitter; however, the physiological role(s) of this endogenous released polyamine is still to be determined. We investigated its cognitive effect in an inhibitory avoidance task in adult rats. Agmatine (0.1, 1, 10, and 20 mg/kg) or saline was administered ip immediately after training or 1 h before testing. Posttraining injection of agmatine facilitated (p0.05) memory consolidation in this task; however pretest treatment showed no effect on retrieval (p0.05). We suggest that the facilitatory effect of agmatine on memory consolidation in inhibitory avoidance task might be mediated through the activation of the locus coeruleus.

To assess safety and clinical efficacy of the nondamaging photothermal therapy for the macula for the treatment of chronic central serous retinopathy.Sixteen eyes of 16 patients with persistent central serous retinopathy (4 months of duration) were treated with the PASCAL Streamline) at 577-nm wavelength, using 200-μm retinal spot sizes. Using Endpoint Management Software, the laser power was first titrated for a barely visible burn with 15-ms pulses, which was defined as 100% pulse energy. Treatment was then applied over the area of serous retinal detachment and adjacent nonthickened retina, using 30% pulse energy with the spot spacing of 0.25 beam diameter. Changes in subretinal fluid, Early Treatment Diabetic Retinopathy Study best-corrected visual acuity, and central macular thickness were measured over 6 months of follow-up. Pretreatment and posttreatment fluorescein angiography and fundus autofluorescence were also assessed.On average, 532 spots have been applied per treatment. No visible laser marks could be detected by clinical observation, optical coherence tomography, fundus autofluorescence, or fluorescein angiography. On average, 12 Early Treatment Diabetic Retinopathy Study letters gain was achieved at 2 months and was sustained by 6 months (P0.001). Central macular thickness decreased from 350 μm to 282 μm (P = 0.004). Subretinal fluid completely resolved in 37% of the patients after first treatment, whereas 44% of the patients required retreatment after 3 months because of recurrent fluid or incomplete resolution. The remaining 19% of the patients received a second retreatment. By 6 months, in 75% of the patients, the subretinal fluid was completely resolved, whereas in 25%, there was some minimal fluid left.Photothermal therapy using 577-nm PASCAL laser with Endpoint Management graphic user interface was safe, and it improved visual acuity and resolution of subretinal fluid in chronic central serous retinopathy. Lack of tissue damage allows periodic retreatment without cumulative scaring, characteristic to conventional photocoagulation. This technique should be tested in the treatment of other macular disorders and may offer an alternative to conventional laser coagulation of the macula and to anti-vascular endothelial growth factor pharmacological treatments of macular diseases.

Retinal photocoagulation typically results in permanent scarring and scotomata, which limit its applicability to the macula, preclude treatments in the fovea, and restrict the retreatments. Non-damaging approaches to laser therapy have been tested in the past, but the lack of reliable titration and slow treatment paradigms limited their clinical use. We developed and tested a titration algorithm for sub-visible and non-damaging treatments of the retina with pulses sufficiently short to be used with pattern laser scanning. The algorithm based on Arrhenius model of tissue damage optimizes the power and duration for every energy level, relative to the threshold of lesion visibility established during titration (and defined as 100%). Experiments with pigmented rabbits established that lesions in the 50-75% energy range were invisible ophthalmoscopically, but detectable with Fluorescein Angiography and OCT, while at 30% energy there was only very minor damage to the RPE, which recovered within a few days. Patients with Diabetic Macular Edema (DME) and Central Serous Retinopathy (CSR) have been treated over the edematous areas at 30% energy, using 200μm spots with 0.25 diameter spacing. No signs of laser damage have been detected with any imaging modality. In CSR patients, subretinal fluid resolved within 45 days. In DME patients the edema decreased by approximately 150μm over 60 days. After 3-4 months some patients presented with recurrence of edema, and they responded well to retreatment with the same parameters, without any clinically visible damage. This pilot data indicates a possibility of effective and repeatable macular laser therapy below the tissue damage threshold.

CNS neurons change their connectivity to accommodate a changing environment, form memories, or respond to injury. Plasticity in the adult mammalian retina after injury or disease was thought to be limited to restructuring resulting in abnormal retinal anatomy and function. Here we report that neurons in the mammalian retina change their connectivity and restore normal retinal anatomy and function after injury. Patches of photoreceptors in the rabbit retina were destroyed by selective laser photocoagulation, leaving retinal inner neurons (bipolar, amacrine, horizontal, ganglion cells) intact. Photoreceptors located outside of the damaged zone migrated to make new functional connections with deafferented bipolar cells located inside the lesion. The new connections restored ON and OFF responses in deafferented ganglion cells. This finding extends the previously perceived limits of restorative plasticity in the adult retina and allows for new approaches to retinal laser therapy free of current detrimental side effects such as scotomata and scarring.

Purpose: To study healing of retinal laser lesions in patients undergoing PRP using SD-OCT. Methods: Moderate, light and barely visible retinal burns were produced in patients with proliferative diabetic retinopathy scheduled for PRP using 100-, 20- and 10-ms pulses of 532-nm laser, with retinal spot sizes of 100, 200 and 400 μm. Lesions were measured with OCT at 1 hr, 1 week, 1, 2, 4, 6, 9 and 12 months. OCT imaging was correlated with histology in a separate study in rabbits. Results: Lesions produced by the standard 100-ms exposures exhibited steady scarring, with the damage zone stabilized after 2 months. For 400- and 200-μm spots and 100-ms pulses, the residual scar area at 12 months was approximately 50% of the initial lesion size for moderate, light and barely visible burns. In contrast, lesions produced by shorter exposures demonstrated enhanced restoration of the photoreceptor layer, especially in smaller burns. With 20-ms pulses, the damage zone decreased to 32%, 24% and 20% for moderate, light and barely visible burns of 400 μm, respectively, and down to 12% for barely visible burns of 200 μm. In the 100-μm spots, the residual scar area of the moderate 100-ms burns was 41% of the initial lesion, while barely visible 10-ms burns contracted to 6% of the initial size. Histological observations in rabbits were useful for proper interpretation of the damage zone boundaries in OCT. Conclusions: Traditional photocoagulation parameters (400 μm, 100 ms and moderate burn) result in a stable scar similar in size to the beam diameter. Restoration of the damaged photoreceptor layer in lighter lesions produced by shorter pulses should allow reducing the common side-effects of photocoagulation such as scotomata and scarring.

Application of femtosecond lasers to cataract surgery has added unprecedented precision and reproducibility but ocular safety limits for the procedure are not well-quantified. We present an analysis of safety during laser cataract surgery considering scanned patterns, reduced blood perfusion, and light scattering on residual bubbles formed during laser cutting. Experimental results for continuous-wave 1030 nm irradiation of the retina in rabbits are used to calibrate damage threshold temperatures and perfusion rate for our computational model of ocular heating. Using conservative estimates for each safety factor, we compute the limits of the laser settings for cataract surgery that optimize procedure speed within the limits of retinal safety.

Over a million people in US alone are visually impaired due to the neovascular form of age-related macular degeneration (AMD). The current treatment is monthly intravitreal injections of a protein which inhibits Vascular Endothelial Growth Factor, thereby slowing progression of the disease. The immense financial and logistical burden of millions of intravitreal injections signifies an urgent need to develop more long-lasting and cost-effective treatments for this and other retinal diseases. Viral transfection of ocular cells allows creation of a “biofactory” that secretes therapeutic proteins. This technique has been proven successful in non-human primates, and is now being evaluated in clinical trials for wet AMD. However, there is a critical need to down-regulate gene expression in the case of total resolution of retinal condition, or if patient has adverse reaction to the trans-gene products. The site for genetic therapy of AMD and many other retinal diseases is the retinal pigment epithelium (RPE). We developed and tested in pigmented rabbits, an optical method to down-regulate transgene expression in RPE following vector delivery, without retinal damage. Microsecond exposures produced by a rapidly scanning laser vaporize melanosomes and destroy a predetermined fraction of the RPE cells selectively. RPE continuity is restored within days by migration and proliferation of adjacent RPE, but since the transgene is not integrated into the nucleus it is not replicated. Thus, the decrease in transgene expression can be precisely determined by the laser pattern density and further reduced by repeated treatment without affecting retinal structure and function.