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Purpose To evaluate the effects of intravitreal injection of tissue plasminogen activator (tPA) and gas vs. pars plana vitrectomy (PPV) surgery as first-line treatment for subretinal hemorrhage. Methods Retrospective study of 107 adults treated for subretinal hemorrhage at a tertiary hospital during 2008–2019; 51 received injection of tPA and gas and 56 underwent PPV. Results No between-group differences were found in age and sex, medical history, use of anticoagulants or antiplatelets, history of ocular surgeries, and previous use of intravitreal anti-VEGF. Overall follow-up time was longer in the PPV group (median 4.9 vs 3.28 years, p = 0.005). The hemorrhage was displaced in a similar percentage of patients in the tPA-and-gas group (n = 40, 78.4%) and the PPV group (n = 45, 80.4%) (p = 0.816). Approximately 80% of patients in the tPA-and-gas group were able to forgo PPV surgery. Visual acuity (in LogMAR) was similar in the two groups prior to the diagnosis of subretinal hemorrhage but better in the tPA-and-gas group at the end of follow-up (p Conclusion Injection of gas and tPA can be done immediately following diagnosis of subretinal hemorrhage as an office procedure. Visual acuity outcome is good, with a high rate of blood displacement. About 20% of patients might require additional PPV as secondary intervention.

Purpose To compare morphologic characteristics of type 1 macular neovascularization (MNV) flow pattern in treatment-naïve and previously treated patients with age-related macular degeneration (AMD) as assessed by optical coherence tomography angiography (OCTA). Study Design Cross-sectional study Materials and Methods Macular OCT angiography images were acquired using RTVue XR Avanti with AngioVue. Distinct morphologic biomarkers and quantifiable features of the neovascular membranes were studied on en-face projection images comparing treatment-naïve and previously treated patients. Results The study included 68 eyes of 58 patients. Among them, 24 eyes were treatment-naïve, and the remaining eyes had received a mean of 19.6 injections. Immature lesions were more associated with treatment-naïve eyes and hyper-mature lesions were associated with previously treated eyes (p = 0.005). Tangle pattern was associated with treatment-naïve eyes (p = 0.013), whereas mature core vessels and sea fan pattern were associated more with previously treated eyes (p = 0.001 and p = 0.044, respectively). Vascular density of the neovascular membrane was higher in the treatment-naïve group (p = 0.036) and the average MNV area was similar between the 2 groups (p = 0.683). Conclusions Based on OCTA, morphologic biomarkers of type 1 MNV might be an indication of previous treatment. The MNV pattern can improve our understanding of its maturation under anti-VEGF treatment and might be valuable to better guide therapeutic decisions and provide more personalized care to patients with AMD.

To assess the normal healing process of limbal–conjunctival autograft (LCA) after pterygium removal during the early postoperative period using anterior segment optical coherence tomography angiography (OCTA). Prospective case series of seven patients undergoing pterygium removal with LCA transplantation procedure, imaged with anterior segment OCTA, and anterior segment colour photos prior to the procedure and on postoperative day (POD) 1, 3, 7 and 30. Revascularization of the graft was analysed quantitatively and qualitatively to estimate patterns of blood vessel growth. Association between revascularization to graft thickness was also investigated. On POD 1, all autografts showed either minimal flow signal or no signal at all (Mean 7.1 ± 3.3%). Regrowth of blood vessels into the graft was detected on OCTA scans on POD3 (8.7 ± 3.6%) to 7 (14.3 ± 4.1%), as nonorganised vessels formation in their appearance. Blood vessels were seen growing in a centrifugal pattern towards the surrounding conjunctiva, originating from the underlying episcleral vessels. Revascularization flow signal was seen throughout nearly all graft extent on day 30 (21.6 ± 2.2%). Graft oedema was evident on the first week (Mean 611 ± 120 μm, 695 ± 84 μm, 639 ± 96 μm of POD 1, 3 and 7, respectively), reducing substantially by day 30 (300 ± 108 μm). OCTA imaging can be used to assess the LCA healing process during the early postoperative period. Revascularization occurring as early as 3–7 days post-surgery, seems to originate from the underlying episcleral vessels. Therefore, careful handling of the bare scleral surface during surgery may be prudent for achieving an adequate healing process.

Background As intravitreal anti-VEGF injections became the mainstay of treatment for many retinal diseases, the cause of a secondary sustained elevated intraocular pressure is still unclear. The aim of our study was to study the clearance of Aflibercept from the anterior chamber angle, in a rat model, to test if an aggregation exists. Methods Choroidal neovascular lesions (CNV) were induced in the right eye of 12 brown Norway rats, using indirect laser ophthalmoscope. Intravitreal Aflibercept injection (0.12 mg/3 µl) was performed 3 days after CNV induction. Rats were euthanized at predetermine time intervals of 3, 6, 24 and 48 h post injection, with immediate enucleation for histological analysis with H&E and immunofluorescence staining. Aflibercept molecules were stained with red fluorescence thanks to the formation of the immune complex Aflibercept-Rabbit anti human IgG-Anti rabbit antibodies-Cy3. Results Immediately after the injection, a strong fluorescence signal was detected, indicating the presence of Aflibercept in the iridocorneal angle. At 3- and 6-h interval a strong signal of Aflibercept was still seen. Six hours post injection, the signal was highly concentrated in Schlemm’s canal. In the 2 eyes harvested 24 h post Aflibercept injection, red fluorescence signal intensity was decreased in one eye, occupying mainly intra scleral venous plexuses, and absent in the other eye. At 48 h there was no fluorescence signal, confirming complete clearance of Aflibercept. Conclusions In our rat model, a complete clearance of Aflibercept from the anterior chamber angle, was seen 48 h after the injection. This finding refutes the theory of possible connection between IOP elevation and mechanical obstruction. Evacuation time of Aflibercept through the angle is of the same magnitude as that of Bevacizumab in the same rat model.

Lymphatic-venous malformations (LVMs) are development defects that result in abnormal connections between the lymphatic and venous systems. The authors describe a 7-weeks-old female infant who presented with a right orbital LVM extending to the ipsilateral cheek and subconjunctiva of the right eye, intracranial developmental venous anomalies in the right cerebellum, and a significant right eye intraocular retinal vascular malformation. Since orbital LVM is usually diagnosed in infancy or childhood, pediatric ophthalmologists should actively look for intraocular vascular malformations as such findings can poorly affect a patient’s vision.

Purpose: To estimate the extent of WhatsApp utilization using text and media messages for inter-physician consultations among ophthalmologists (residents and specialists) at various clinical settings and its perceived benefits for ophthalmologists and their patients. We also aimed to detect obstacles that concern ophthalmologists when using WhatsApp as a consultation platform. Methods: This was a cross-sectional study using a self-administered survey through Google Forms, which was sent to 660 practicing ophthalmologists during April to May 2020. Results: One hundred and ninety-two ophthalmologists completed the questionnaire, 151 of which (78.6%) were specialists and 41 (21.4%) were residents. Most ophthalmologists reported using WhatsApp at least once a day for both personal and professional use. Residents reported lower rates of contacting patients using WhatsApp than specialists (1.51 ± 0.98 vs 2.72 ± 1.32, p Conclusion: Many ophthalmologists already use WhatsApp as a tool for professional consultations with other providers, mainly thanks to its simplicity and wide availability. Residents use it more frequently than specialists, and ranked it higher when asked how much WhatsApp has improved the clinical setting. Policy makers should address concerns brought up by physicians, such as documentation in medical records and proper compensation for consulting ophthalmologists during and after work hours.

Introduction: The purpose of this study is to evaluate the effect of intravitreal injection of tissue plasminogen activator (tPA) on proliferative vitreoretinopathy (PVR). Methods: PVR was induced in a rabbit model by intraocular injection of dispase (0.05 U/0.1 mL). Progression of PVR was followed by indirect ophthalmic examination. Following 6 weeks, five animals received intravitreal injection of 25 µg/0.1 mL tPA and four were injected with balanced salt solution (BSS). Animals were euthanized at 48 hours following tPA/BSS injection and eyes were enucleated for histological evaluation and staining with α-smooth muscle actin (αSMA) and Sirius Red. Results: Following tPA injection, one eye had a reduction in PVR from grade 2 to 1 and three eyes remained stable. Following BSS, PVR grade was unchanged in three eyes. In one eye in each group, the severity of PVR couldn't be assessed due to limited view. Staining with αSMA showed reduced presence of fibroblasts in eyes injected with tPA compared with those injected with BSS. Collagen type I and III, demonstrated by Sirius Red staining, was reduced in the tPA group in comparison to controls. Conclusion: Our results suggest that intravitreally injected tPA may show an inhibitory effect on PVR progression. Further exploration in clinical trials is desired.

Purpose To evaluate multimodal imaging findings of solitary idiopathic choroiditis (SIC; also known as unifocal helioid choroiditis) to clarify its origin, anatomic location, and natural course. Design Multicenter retrospective observational case series. Participants Sixty-three patients with SIC in 1 eye. Methods Demographic and clinical data were collected. Multimodal imaging included color fundus photography, OCT (including swept-source OCT), OCT angiography (OCTA), fundus autofluorescence, fluorescein and indocyanine green angiography, and B-scan ultrasonography. Main Outcome Measures Standardized grading of imaging features. Results Mean age at presentation was 56 ± 15 years (range, 12–83 years). Mean follow-up duration in 39 patients was 39 ± 55 months (range, 1 month–25 years). The lesions measured a mean of 2.4 × 2.1 mm in basal diameter, were located inferior (64%) or nasal to the optic disc, and appeared yellow (53%). No systemic associations were found. The lesions all appeared as an elevated subretinal mass, with OCT demonstrating all lesions to be confined to the sclera, not the choroid. On OCT, the deep lesion margin was visible in 12 eyes with a mean lesion thickness of 0.6 mm. Overlying choroidal thinning or absence was seen in 95% (mean choroidal thickness, 28 ± 35 μm). Mild subretinal fluid was observed overlying the lesions in 9 patients (14%). Retinal pigment epithelial disruption and overlying retinal thinning was observed in 56% and 57%, respectively. OCT angiography was performed in 13 eyes and demonstrated associated choroidal and lesional flow voids. Four lesions (6%) were identified at the macula, leading to visual loss in 1 patient. One lesion demonstrated growth and another lesion showed spontaneous resolution. Conclusions In this largest series to date, multimodal imaging of SIC demonstrated a scleral location in all patients. The yellow and white clinical appearance may be related to scleral unmasking resulting from atrophy of overlying tissues. Additional associated features included documentation of deep margin on swept-source OCT, trace subretinal fluid in a few patients, and OCTA evidence of lesional flow voids. Because of the scleral location of this lesion in every patient, a new name, focal scleral nodule, is proposed.

Purpose To investigate the safety of face masks worn by patients during intravitreal injections. Methods A prospective, qualitative, interventional study performed in a tertiary university hospital. Healthy volunteers were asked to wear three different professional surgical face masks while air leaks around the eyes were monitored. Three types of masks were investigated as follows: 1) surgical face mask with four tying strips, 2) surgical face mask with elastic ear loops and 3) 2200 N95 tuberculosis particulate face mask. For each session the periocular area was inspected for air leak during normal respiration, speech, and deep respiration. Detection of air leak was performed using the following two professional thermal cameras: FLIR A310-thermal camera and EyeCGas 2.0-super sensitive infrared camera used for detection of minute fugitive emissions of industrial gases. Results Ten healthy volunteers were enrolled in this study. The experiment was repeated 45 times for each camera; 3 times for each of 3 mask types, on 5 volunteers, for a total of 90 trials. Air jets were detected originating from the superior edges of the masks radiating toward the eyes in 81% (73/90) of cases in total; 71% (32/45) with the FLIR camera and 91% (41/45) with the OPGAL camera. Air leaks were detected with all investigated mask types. Conclusion Patients wearing face masks during intravitreal injections may be at a higher risk of endophthalmitis. Until further data are available, we recommend verifying proper face mask fitting and either taping the upper edges of the face masks with a medical adhesive tape or using an adhesive surgical drape around the injected eye.

Purpose To describe the clinical characteristics and treatment of spontaneous Descemet membrane (DM) detachment occurring decades after penetrating keratoplasty (PK). Methods A multicenter interventional case series design was used. We reviewed the medical records of 4 patients with a history of PK presenting with spontaneous DM detachment at 3 university hospitals in Israel and an ocular surgery institute in The Netherlands in 2016 to 2019. Patient demographic and clinical data, postoperative best corrected visual acuity, findings on preoperative and postoperative anterior segment optical coherence tomography (AS-OCT), and graft survival were recorded. Results Patients were aged 46 to 50 years. All had undergone PK for keratoconus 20 to 26 years previously. Patients presented within 18 to 180 days of onset of visual disturbance. Symptoms included sudden painless visual loss (2 patients), gradual visual loss and foreign body sensation (1 patients), and visual loss not otherwise specified (1 patient). Slit-lamp examination showed corneal edema, and AS-OCT showed DM detachment of variable extent. In 2 patients, the initial diagnosis was graft rejection and failure. Treatment consisted of anterior chamber injection of air (n = 3) or 20% SF6 (n = 1). In 3 patients, the DM reattached and the cornea regained its clarity. The fourth patient had persistent DM detachment that required repeated PK. Conclusions Spontaneous DM detachment can mimic late graft failure in patients after PK. If diagnosed early, DM reattachment may be performed by air/gas injection, avoiding repeated keratoplasty. Eyes with presumed late penetrating graft rejection or failure should be examined by AS-OCT to exclude DM detachment.

BACKGROUND AND OBJECTIVE: To assess the foveal microvascular structure of children with retinopathy of prematurity (ROP) treated with diode laser photocoagulation using optical coherence tomography angiography (OCTA). PATIENTS AND METHODS: OCTA was performed at a tertiary medical center in 17 children (27 eyes) aged 4 to 16 years with a history of diode laser photocoagulation treated ROP. OCTA parameters were compared with those of 12 healthy age-matched controls (23 eyes) attending the orthoptics clinic and correlated with clinical factors. RESULTS: Compared with controls, the ROP group had a smaller foveal avascular zone area ( P < .001), lower deep vascular plexus density ( P < .001), lower flow density ( P = .025), and greater central macular thickness ( P < .001). High intraventricular hemorrhage grade correlated with smaller foveal avascular zone area ( P = .008) and greater inner macular thickness ( P = .047). There was no impact of gestational age, birth weight, or refractive status. CONCLUSION: OCTA can identify significant quantifiable long-term macular microvascular and structural changes in this patient population. [ Ophthalmic Surg Lasers Imaging Retina . 2022;53(4):194–201.]

Eye trauma is an unfortunate and often preventable cause of vision loss. Confetti cannons are common causes of injury. Awareness of ocular hazards of confetti cannons remains low because of limited reports describing ophthalmic injuries following their use.To describe outcomes of ocular trauma caused by confetti cannons and to increase recognition of their ocular risks.A retrospective analysis was conducted of eye injuries caused by confetti cannons presenting to a single medical center between 2016 and 2020. Data collected included age, gender, eye injured, ocular damage, visual outcome, and details of surgeries performed.Overall, six consecutive patients (2 males, mean age 19.5 ± 9.74 years) were identified and studied. In all patients only one eye was injured (3 right eyes) during a private celebration, most commonly (n=5) to a bystander while in the vicinity of a cannon operated by someone else. Most common eye injuries included corneal erosion (n=4), traumatic hyphema (n=4), and retinal edema (n=3). Mean initial logMAR visual acuity in the injured eye was 0.73 ± 0.18, improving to 0.25 ± 0.16 at the final visit (P = 0.125). Two patients underwent eye surgery due to their trauma: one to repair globe penetration and another to undergo intravitreal injection of tissue plasminogen activator and C3F8 for submacular hemorrhage, followed 8 months later by intravitreal bevacizumab injection for choroidal neovascularization.Confetti cannons pose hazards that can cause severe ocular trauma resulting in permanent vision loss. Increasing awareness of device hazards is necessary to prevent eye injuries.

Purpose To report an unusual case of an elderly patient with transient outer retinal disruption resembling bilateral multiple evanescent white dot syndrome. Methods Observational case report. Fundus photographs, fluorescein angiography, standard and ultra-widefield fundus autofluorescence, and cross-sectional and en face optical coherence tomography were used to characterize and describe the clinical findings. Results A 67-year-old woman presented with decreased vision and floaters in her left eye. Best-corrected visual acuity was 20/20-3 in the right eye and 20/80-2 in the left eye. Funduscopic examination showed small deep white dots and foveal granularity of the left eye corresponding to hyperautofluorescent spots on fundus autofluorescence and ellipsoid zone disruption on spectral domain optical coherence tomography. The asymptomatic right eye had evidence of subretinal deposits on spectral domain optical coherence tomography but was otherwise unremarkable. At 4-week follow-up, the patient noted resolution of her symptoms in the left eye but had developed floaters and blurry vision in her right eye. The left eye showed resolving white spots and ellipsoid zone disruption. However, the right eye had new evidence of white spots corresponding to hyperautofluorescent spots on fundus autofluorescence. Spectral domain optical coherence tomography demonstrated subretinal deposits overlying areas of ellipsoid zone disruption. At 8-week follow-up, the patient was asymptomatic in both eyes with best-corrected visual acuity of 20/20 in both eyes. The hyperautofluorescent spots on ultra-widefield fundus autofluorescence had faded with restoration of ellipsoid zone disruption in both eyes and disappearance of subretinal deposits. Conclusion Our case demonstrates multimodal retinal imaging findings resembling multiple evanescent white dot syndrome in an elderly patient. The bilateral presentation, presence of subretinal deposits before symptom onset, and older age of the patient were atypical features for this entity.

Purpose To evaluate the intraoperative use of ultrasound biomicroscopy (UBM) during Descemet's membrane endothelial keratoplasty (DMEK) to determine graft's orientation. Methods Prospective interventional study of eight eyes of seven patients who underwent DMEK. Following the identification of correct graft orientation using 'Blue cannula tip' sign during DMEK surgery, UBM was used to ascertain graft's orientation. The rate of successful DMEK graft orientation determined by the UBM was registered and verified postoperatively by anterior segment-optical coherence tomography (OCT). Intra- and postoperative complications, postoperative clearance of the cornea, corrected distance visual acuity and endothelial cell loss were also noted. Results The study included five males and two females aged 54-82 years with corneal oedema due to Pseudophakic bullous keratopathy (n = 5), Fuchs' endothelial dystrophy (n = 2). In all cases, the technique allowed proper determination of the graft's orientation. In one case, 'blue cannula tip' sign showed correct orientation while UBM identified an upside-down graft. The graft was inverted in the anterior chamber using fluid jets, and repeat 'blue cannula tip' sign and UBM examination both showed correct orientation. In all cases, postoperative anterior segment-OCT demonstrated correct graft orientation. Conclusions Use of intraoperative UBM to determine graft orientation during DMEK correlated with proper graft orientation, as was verified postoperatively by anterior segment-OCT. The use of UBM can be particularly helpful in cases of poor graft visibility due to opaque corneal stroma, pigment or blood in the anterior chamber during surgery, or when the blue tint of the graft fades rapidly, which may preclude proper determination of graft's orientation.

To describe the fibrillar architecture of the posterior cortical vitreous and identify variations across eyes of different axial lengths in vivo. Sixty-four eyes of 32 subjects were examined with swept-source optical coherence tomography (SS-OCT). Grading of vitreous degeneration, presence of vitreous cisterns/lacunae, posterior hyaloid status, directionality of vitreous fibers and their relations to vitreous spaces, and lamellar reflectivity of the posterior vitreous were assessed. A consistent pattern of fibrillar organization was discovered. Eyewall parallel fibers formed a dense meshwork over the retinal surface and fibers oriented in a perpendicular fashion to this meshwork were found to envelop the various vitreous spaces, intersecting at variable angles of insertion to the eyewall parallel fibers. Lamellar reflectivity suggestive of splitting of the cortical fibrillar meshwork was detected in 27 eyes (42%) with 56% of these eyes demonstrating perpendicularly oriented intersecting fibers. Fifty-six percent of eyes with lamellar reflectivity had an axial length > 25 mm. SS-OCT imaging revealed fibrillar organization of the posterior vitreous. Eye wall parallel hyperreflectivity of cortical vitreous was a universal finding. This pattern is suggestive of a splitting of cortical vitreous tissue and may represent a precursor to vitreoschisis. Perpendicular fibers appear to be important constituents of the walls of the various liquid vitreous spaces.

Aim: To compare the efficacy of aflibercept (Eylea®), a potent antivascular endothelial growth factor (VEGF) agent, with betamethasone (Celestone®) and placebo for the treatment of formed corneal neovascularization in a rabbit model. Methods: A central corneal chemical burn was created in the right eye of 24 New Zealand albino rabbits. Four weeks later, the rabbits were randomly divided into 4 equal groups for subconjunctival injection of aflibercept, betamethasone, aflibercept+ betamethasone, or saline (control). Digital photographs taken at weekly intervals were rated by 2 masked observers for extent, centricity, and density of corneal neovascularization according to a predefined scale. The percentage of corneal surface involved by neovascularization was quantified by image analysis software (Fiji-J). The change in corneal neovascularization from treatment administration (4 weeks after injury) to 4 weeks later (8 weeks after injury) was assessed. The rabbits were then euthanized, and their eyes were enucleated and processed for histopathological and immunofluorescence studies. Results: There was no significant difference in the change in corneal neovascularization after treatment among the 4 groups according to the digital images (p > 0.15) or histological evaluation with hematoxylin and eosin (p > 0.08). On immunofluorescence assay, a lower VEGF concentration was observed in all treatment groups compared to the control group. Conclusions: In this rabbit model, corneal neovascularization induced by chemical burn failed to regress with treatment with aflibercept, betamethasone, or their combination.

Purpose To survey Friedman lipid globules by high-resolution histologic examination and to compare with multimodal imaging of hyporeflective caverns in eyes with geographic atrophy (GA) secondary to age-related macular (AMD) and other retinal diseases. Design Histologic survey of donor eyes with and without AMD. Clinical case series with multimodal imaging analysis. Participants Donor eyes (n = 139; 26 with early AMD, 13 with GA, 40 with nAMD, 52 with a healthy macula, and 8 with other or unknown characteristics) and 41 eyes of 28 participants with GA (n = 16), nAMD (n = 8), Stargardt disease (n = 4), cone dystrophy (n = 2), pachychoroid spectrum (n = 6), choroidal hemangioma (n = 1), and healthy eyes (n = 4). Methods Donor eyes were prepared for macula-wide epoxy resin sections through the foveal and perifoveal area. In patients, caverns were identified as nonreflective spaces on OCT images. Multimodal imaging included color and red-free fundus photography; fundus autofluorescence; fluorescein and, indocyanine green angiography; OCT angiography; near-infrared reflectance; and confocal multispectral (MultiColor [Spectralis, Heidelberg Engineering, Germany]) imaging. Main Outcome Measures Presence and morphologic features of globules, and presence and appearance of caverns on multimodal imaging. Results Globules were found primarily in the inner choroidal stroma (91.0%), but also localized to the sclera (4.9%) and neovascular membranes (2.1%). Mean diameters of solitary and multilobular globules were 58.9±37.8 μm and 65.4±27.9 μm, respectively. Globules showed morphologic signs of dynamism including pitting, dispersion, disintegration, and crystal formation. Evidence for inflammation in the surrounding tissue was absent. En face OCT rendered sharply delimited hyporeflective areas as large as choroidal vessels, frequently grouped around choroid vessels or in the neovascular tissue. Cross-sectional OCT revealed a characteristic posterior hypertransmission. OCT angiography showed absence of flow signal within caverns. Conclusions Based on prior literature documenting OCT signatures of tissue lipid in atheroma and nAMD, we speculate that caverns are lipid rich. Globules, with similar sizes and tissue locations in AMD and healthy persons, are candidates for histologic correlates of caverns. The role of globules in chorioretinal physiologic features, perhaps as a lipid depot for photoreceptor metabolism, is approachable through clinical imaging.

BackgroundTo investigate the long-term visual and optical coherence tomography (OCT) anatomical outcomes of type 3 neovascularisation (NV) and to identify any baseline predictors of poor outcomes.MethodsIn this retrospective study, patients diagnosed with treatment naïve type 3 NV were identified and categorised into two groups: good or poor vision based on final vision at 1 year. Baseline demographic features and visual acuity (VA) and baseline and 1-year spectral domain OCT (SD-OCT) anatomical findings were studied and correlated with good versus poor visual outcomes.ResultsTen of 25 eyes were classified as having a poor visual outcome (20/50 or worse) at 1 year. Increased age (P=0.049), male gender (p=0.041) and worse baseline VA (ρs=0.61, p=0.001) were associated with poor vision at 1 year. Greater foveal atrophy was noted at 1 year in the poor visual outcome group (p=0.030). Subretinal hyper-reflective material and choroidal thinning were additional features noted more commonly in this group.ConclusionIncreased age, male gender and lower baseline vision may be important baseline predictors of poor visual outcomes in eyes with type 3 NV. The development of central outer retinal atrophy and fibrosis, as identified with SD-OCT, may limit long-term vision in eyes with type 3 NV.

Purpose To define the range and life cycles of cuticular drusen phenotypes using multimodal imaging and to review the histologic characteristics of cuticular drusen. Design Retrospective, observational cohort study and experimental laboratory study. Participants Two hundred forty eyes of 120 clinic patients with a cuticular drusen phenotype and 4 human donor eyes with cuticular drusen (n = 2), soft drusen (n = 1), and hard drusen (n = 1). Methods We performed a retrospective review of clinical and multimodal imaging data of patients with a cuticular drusen phenotype. Patients had undergone imaging with various combinations of color photography, fluorescein angiography, indocyanine green angiography, near-infrared reflectance, fundus autofluorescence, high-resolution OCT, and ultrawide-field imaging. Human donor eyes underwent processing for high-resolution light and electron microscopy. Main Outcome Measures Appearance of cuticular drusen in multimodal imaging and the topography of a cuticular drusen distribution; age-dependent variations in cuticular drusen phenotypes, including the occurrence of retinal pigment epithelium (RPE) abnormalities, choroidal neovascularization, acquired vitelliform lesions (AVLs), and geographic atrophy (GA); and ultrastructural and staining characteristics of druse subtypes. Results The mean age of patients at the first visit was 57.9±13.4 years. Drusen and RPE changes were seen in the peripheral retina, anterior to the vortex veins, in 21.8% of eyes. Of eyes with more than 5 years of follow-up, cuticular drusen disappeared from view in 58.3% of eyes, drusen coalescence was seen in 70.8% of eyes, and new RPE pigmentary changes developed in 56.2% of eyes. Retinal pigment epithelium abnormalities, AVLs, neovascularization, and GA occurred at a frequency of 47.5%, 24.2%, 12.5%, and 25%, respectively, and were significantly more common in patients older than 60 years of age (all P P Conclusions Although the ultrastructural characteristics of cuticular drusen appear more similar to those of hard drusen, their lifecycle and macular complications are more comparable with those of soft drusen. Cuticular drusen phenotype may confer a unique risk for the development of GA and neovascularization.

The term aneurysmal type 1 neovascularization is derived from terminology, which is established in the literature but has fallen out of use. We believe that aneurysmal type 1 neovascularization accurately describes the lesions which define the entity known as polypoidal choroidal vasculopathy (PCV). Over the last three decades, the clinical spectrum of PCV has expanded to recognize the occurrence of the aneurysmal (polypoidal) lesions in different contexts, resulting in a complex and unwieldy taxonomy based sometimes on circumstantial findings rather than mechanistic considerations. Advances in multimodal imaging provides increasingly convincing evidence that the lesions which define various forms of PCV are indeed vascular and arise from type 1 neovascular networks. The understanding of PCV as type 1 neovascularization with aneurysms renews focus on the question as to why some patients with type 1 neovascularization develop aneurysms while others do not. Conceptual themes and potential for further study are discussed.

To evaluate multimodal imaging findings of solitary idiopathic choroiditis (SIC; also known as unifocal helioid choroiditis) to clarify its origin, anatomic location, and natural course.Multicenter retrospective observational case series.Sixty-three patients with SIC in 1 eye.Demographic and clinical data were collected. Multimodal imaging included color fundus photography, OCT (including swept-source OCT), OCT angiography (OCTA), fundus autofluorescence, fluorescein and indocyanine green angiography, and B-scan ultrasonography.Standardized grading of imaging features.Mean age at presentation was 56 ± 15 years (range, 12-83 years). Mean follow-up duration in 39 patients was 39 ± 55 months (range, 1 month-25 years). The lesions measured a mean of 2.4 × 2.1 mm in basal diameter, were located inferior (64%) or nasal to the optic disc, and appeared yellow (53%). No systemic associations were found. The lesions all appeared as an elevated subretinal mass, with OCT demonstrating all lesions to be confined to the sclera, not the choroid. On OCT, the deep lesion margin was visible in 12 eyes with a mean lesion thickness of 0.6 mm. Overlying choroidal thinning or absence was seen in 95% (mean choroidal thickness, 28 ± 35 μm). Mild subretinal fluid was observed overlying the lesions in 9 patients (14%). Retinal pigment epithelial disruption and overlying retinal thinning was observed in 56% and 57%, respectively. OCT angiography was performed in 13 eyes and demonstrated associated choroidal and lesional flow voids. Four lesions (6%) were identified at the macula, leading to visual loss in 1 patient. One lesion demonstrated growth and another lesion showed spontaneous resolution.In this largest series to date, multimodal imaging of SIC demonstrated a scleral location in all patients. The yellow and white clinical appearance may be related to scleral unmasking resulting from atrophy of overlying tissues. Additional associated features included documentation of deep margin on swept-source OCT, trace subretinal fluid in a few patients, and OCTA evidence of lesional flow voids. Because of the scleral location of this lesion in every patient, a new name, focal scleral nodule, is proposed.

Purpose Cuticular drusen (CD) have been associated with manifestations of age-related macular degeneration such as atrophy and neovascularization in the macula. In this study, eyes with CD were followed and investigated for the estimated 5-year risk of progression to sequelae of age-related macular degeneration such as geographic atrophy (GA) and macular neovascularization (MNV). Methods A consecutive series of patients with CD were followed for the development of GA and MNV. Whenever possible, they were also studied retrospectively. The patients with CD were categorized into three phenotypic groups. Phenotype 1: eyes had concentrated, densely populated CD in the macular and paramacular area, Phenotype 2: eyes showed scattered CD in the posterior fundus, and Phenotype 3: involved eyes with CD mixed with large drusen (>200 µm). The 5-year incidence of progression was then estimated using a Kaplan-Meier estimator. Results A total of 63 eyes from 38 patients (35 women with a mean age at presentation of 58.9 ± 14.2 years) were studied and followed for a mean of 40 ± 18 months. Thirteen patients had single eyes with GA (84.5%; 11/13) or MNV (15.5%; 2/13) in one eye at presentation and were subsequently excluded. Geographic atrophy developed in 19.0% (12/63) of eyes and MNV in 4.8% (3/63) of eyes. The cumulative estimated 5-year risk of GA and MNV was 28.4% and 8.7%, respectively. The estimated 5-year incidence of MNV or GA was 12.6%, 50.0%, and 51.6% in Phenotype 1, Phenotype 2, and Phenotype 3, respectively (P = 0.0015, log-rank test). No difference in risk was found in the development of GA or MNV (P = 0.11) between the subgroup of patients presenting with GA or MNV in their fellow eye and those with both eyes included. Conclusion When patients with CD are followed longitudinally, there was a significant risk of progression to GA or MNV for Phenotype 2 and Phenotype 3. Patients with CD are commonly first diagnosed in the fifth decade of life, and there is a female predominance. Clinicians should use multimodal imaging to detect and be aware of the risk of progression to manifestations of GA and MNV. These risks of GA and MNV suggest that patients with CD may be part of the overall spectrum of age-related macular degeneration.

PURPOSE We aimed to evaluate the efficacy of subconjunctival aflibercept, a vascular endothelial growth factor trap compound, for the treatment of corneal neovascularization in a rat model. METHODS Chemical burn was produced in the central cornea of 31 male Sprague-Dawley rats. Animals were randomized to receive treatment with subconjunctival injection of 0.08 mL aflibercept (25 mg/mL), 0.05 mL bevacizumab (25 mg/mL), or 0.05 mL physiologic saline. Corneal neovascularization was evaluated on postinjury days 1, 3, 7, 9, and 13 by corneal photographs. The rats were killed on day 21 and samples were collected for histological and flat-mount immunofluorescence analyses. RESULTS In all rats, vascular sprouting began on day 3, reached maximum density on days 7-9, and spontaneously regressed thereafter. Mean burn area in the central cornea comprised ∼15% of the total corneal area. The aflibercept group had a significantly smaller relative area of neovascularization than both control group (P < 0.05, 12.27 ± 9.91, 29.66 ± 9.96 days 7) and bevacizumab group (P < 0.05, 12.27 ± 9.91, 21.27 ± 8.19 days 7 and 15.5 ± 10.25, 32.38 ± 9.44 days 9; Mann-Whitney test). On histological study, hematoxylin and eosin staining revealed blood vessels extending to the central cornea in the control and bevacizumab groups and limited to the periphery in the aflibercept group. Immunofluorescence study with an endothelial marker revealed a smaller area of staining in the aflibercept group. CONCLUSIONS Aflibercept effectively inhibits corneal neovascularization in a rat model of chemical burn-induced neovascularization and warrants further study for potential use in humans.

Antivascular endothelial growth factor (Anti-VEGF) agents have been widely used for a variety of ocular disorders. The etiology of sustained ocular hypertension following intravitreal administration of anti-VEGF agents is yet to be unraveled. Our study investigates and characterizes the presence of intravitreally injected bevacizumab in the aqueous outflow channels of a rat model. Choroidal neovascularization (CNV) was induced by diode laser photocoagulation to the right eye of twelve Brown Norway rats. Bevacizumab (25 mg/ml) was injected intravitreally after 3 days. Immediately after bevacizumab injection, and 3, 6, 24 and 48 h later, animals were euthanized for immunofluorescence staining. Donkey anti-human IgG labeled with Alexa Fluor(®) 488 was used for bevacizumab immunoreactivity detection. Anti-CD31 antibody was used as a marker for Schlemm's canal endothelial cells. Untreated eyes were used as negative controls. The intensity of the immunostaining was analyzed qualitatively. Bevacizumab immunoreactivity was found in the aqueous outflow channels including the trabecular meshwork and Schlemm's canal immediately after injection, and declined incrementally within the following hours. Forty-eight hours after the injection, no bevacizumab staining was detected in the aqueous outflow channel structures. Our manuscript demonstrates the presence of bevacizumab in the trabecular meshwork and Schlemm's canal structures after intravitreal injection in a CNV induced rat model. Bevacizumab molecules passed through the aqueous outflow channels within 48 h after intravitreal bevacizumab injection.

Purpose To quantitatively characterize the retinal vascular network in healthy and pathological cases using optical coherence tomography angiography (OCTA) images. Methods The study included 56 eyes of 28 patients as follows: 26 healthy, 20 with diabetic retinopathy (DR), 6 with age-related macular degeneration (AMD), and 4 with retinal vein occlusion (RVO). For 33 eyes (16 healthy and 17 with DR), vessel density maps were provided by the OCTA machine. An automatic algorithm classified the image (as healthy, DR, AMD, or RVO) and provided quantitative information obtained from the angiograms, including global vessel density, global fractal dimension, and fovea avascular zone (FAZ) area. Classification results were compared with the diagnosis made by a retina specialist. The quantitative values were compared with the literature and to values provided by the OCTA machine. Results The success rate of classification was 83.9%. Vessel densities obtained by our algorithm (in healthy and DR cases) were significantly lower than the values reported in previous studies using OCTA. Similarly, they were much lower than the values provided by the OCTA machine. However, vessel densities in the healthy cases were similar to or higher than (depending on the retinal layer) the recently published values that may be considered as gold standard. Our values of fractal dimension were similar to those previously reported. Conclusions Our algorithm provides significantly improved vessel density values compared with previous studies. We believe our algorithm successfully omits false vessels. Translational relevance Accurately assessing retinal vessel density enables better evaluation of retinal disorders.

Purpose To report a retinal pigment epithelium (RPE) tumor with exudative maculopathy, originating from an atypical RPE lesion presumed to represent congenital hypertrophy of the RPE or RPE hyperplasia. Methods Multimodal imaging including fundus autofluorescence, optical coherence tomography, fluorescein angiography, and optical coherence tomography angiography. Results A 76-year-old West African man noted visual acuity reduction to count fingers in the right eye and 20/400 in the left eye. Features of chronic glaucoma were noted. In addition, there was a fairly well-circumscribed darkly pigmented RPE lesion in the paramacular region in the right eye, measuring 4 mm in diameter and flat and consistent with atypical congenital hypertrophy of the RPE or RPE hyperplasia. On the posterior margin of this mass was an RPE tumor, presumed to represent RPE adenoma, producing exudative maculopathy and cystoid macular edema. Multimodal imaging was used to distinguish the RPE tumor from macular neovascularization. A similar atypical congenital hypertrophy of the RPE without retinopathy measuring 3.5mm in diameter was noted in the temporal macular region in the left eye. After six monthly doses of intravitreal bevacizumab (1.25 mg/0.05 mL) in the right eye, the maculopathy resolved and the RPE mass showed partial involution with visual acuity return to baseline 20/200. Conclusion Congenital hypertrophy of the RPE and RPE hyperplasia can produce RPE adenoma with related exudative maculopathy. In this case, the maculopathy responded to bevacizumab.

PURPOSE To evaluate the efficacy of corneal collagen cross-linking (CXL) with photoactivated riboflavin (PACK-CXL) as primary therapy for Staphylococcus aureus-induced corneal ulcers in a rabbit model. METHODS The right eye of 40 rabbits was inoculated with S. aureus to induce formation of central corneal ulcers (day 1). The ulcer was examined on day 5, and rabbits were randomly assigned to 4 groups-group A: no treatment (control); group B: topical antibiotic treatment (cefazolin 50 mg/mL, garamycin 14 mg/mL drops, chloramphenicol 5% ointment every 2 hours); group C: PACK-CXL; group D: PACK-CXL + topical antibiotics. Follow-up by biomicroscopy was performed on day 5 and then every week for 1 month. The main outcome measures included infiltrates or the scar diameter, time to healing, time to full epithelialization, and a change in corneal thickness. RESULTS After 1 month of treatment, group C ulcers had the smallest mean scar diameter (8.8 mm), followed by groups D (11.2 mm), B (13.0 mm), and A (24.5 mm) (P = 0.011). Group C had the shortest mean healing time (15.5 days), followed by groups D (17.2 days), B (19.7 days), and A (21.8 days). Analysis of relative reduction in the infiltrate size from day 5 yielded better results for groups C (P = 0.039) and D (P = 0.034) than those of group B. CONCLUSIONS We demonstrate a beneficial effect of PACK-CXL as primary treatment, either as stand-alone or as an adjuvant to antimicrobial therapy.

BACKGROUND AND OBJECTIVE: To determine whether subretinal fluid drainage (SRF) using perfluorocarbon (PFC) during rhegmatogenous retinal detachment (RRD) repair reduces postoperative metamorphopsia. PATIENTS AND METHODS: Consecutive patients after RRD were evaluated for best-corrected visual acuity (BCVA), funduscopy, and metamorphopsia using M-CHARTS. Fundus autofluorescence and optical coherence tomography were performed. Clinical and operative data were collected. RESULTS: The cohort included 30 patients, of whom 11 (36.7%) underwent intraoperative PFC injection. Rates of macula-off RRD were similar in the two groups (54.5% and 47.4%, P = .705). No association was found between PFC injection and metamorphopsia score. Preoperative macula-off RRD was associated with significantly higher vertical and horizontal metamorphopsia scores than preoperative macula-on. BCVA was significantly worse in the patients with metamorphopsia (logMAR 0.15 vs. logMAR 0.04; P = .042) CONCLUSION: Intraoperative SRF drainage with PFC appears to have no beneficial effect on postoperative metamorphopsia. Metamorphopsia is associated with macular status. [ Ophthalmic Surg Lasers Imaging Retina . 2018;49:e263–e270.]

Purpose: To study choriocapillaris (CC) flow in eyes with Type 3 neovascularization (NV) and age-related macular degeneration, using optical coherence tomography angiography analysis. Methods: In this multicenter, retrospective, observational study, we collected data from 21 patients with unilateral Type 3 NV and age-related macular degeneration, based on clinical examination, structural optical coherence tomography, and fluorescein angiography when available. An additional group of 20 nonneovascular age-related macular degeneration eyes with unilateral Type 1 or Type 2 NV due to age-related macular degeneration was included for comparison. En face optical coherence tomography angiography imaging (3 · 3 mm scans) with quantitative microvascular analysis of the CC was performed. Main outcome measures were: 1) the percent nonperfused choriocapillaris area; and 2) the average CC signal void size. Results: We included 21 patients with unilateral Type 3 NV (15 female, 71.5%) and 20 patients with unilateral Type 1 or 2 NV (9 female, 45.0% P = 0.118). Mean ± SD age was 82.1 ± 7.4 years in the unilateral Type 3 patients and 78.3 ± 8.1 in unilateral Type 1/2 NV subjects (P = 0.392). The percent nonperfused choriocapillaris area was 56.3 ± 8.1% in eyes with Type 3 NV and 51.9 ± 4.3% in the fellow eyes (P = 0.016). The average signal void size was also increased in those eyes with Type 3 NV (939.9 ± 680.9 mm 2 ), compared with the fellow eyes (616.3 ± 304.2 mm 2 , P = 0.039). The number of signal voids was reduced in the Type 3 NV eyes (604.5 ± 282.9 vs. 747.3 ± 195.8, P = 0.046). The subfoveal choroidal thickness was 135.9 ± 54.2 mm in eyes with Type 3 NV and 167.2 ± 65.4 mm in the fellow eyes (P = 0.003). In addition, the fellow eyes of patients with unilateral Type 3 NV displayed more significant CC flow abnormalities versus the fellow eyes with unilateral Type 1/2 NV (percent nonperfused choriocapillaris area = 51.9 ± 4.3% vs. 46.0 ± 2.1%, respectively, P, 0.0001; and average signal void size 616.3 ± 304.2 mm 2 versus 351.4 ± 65.5 mm 2 , respectively, P, 0.0001; and number of signal voids 747.3 ± 195.8 vs. 998.5 ± 147.3, respectively, P, 0.0001). Conclusion: Eyes with unilateral Type 3 NV illustrated increased CC nonperfusion versus fellow nonneovascular eyes. These results suggest that choroidal ischemia may play an important role in the development of Type 3 NV.

Purpose To describe the preclinical and very early stages of type 3 neovascularization using multimodal retinal imaging to expand our understanding of the pathogenesis of this disorder and potentially to prevent late treatment. Design Retrospective cohort study. Participants Patients diagnosed with treatment-naive type 3 neovascularization in the setting of age-related macular degeneration were identified at 4 retina referral centers. Inclusion criteria were: patients older than 55 years with at least 1 OCT and OCT angiography (OCTA) examination before the onset of clinically active type 3 neovascularization (i.e., preclinical stage). Methods Patients underwent a complete ophthalmologic examination including at least OCT and OCTA at the baseline and preclinical stage examinations, and dye angiographies when available. Demographics and clinical findings were analyzed. Main Outcome Measures Description of multimodal imaging features of nascent type 3 neovascularization. Results Fifteen eyes (15 patients; mean age, 83 ± 9 years) were included. At the baseline, mean BCVA was 0.32 ± 0.17 logarithm of the minimum angle of resolution and central macular thickness was 313 ± 50 μm. Preclinical (i.e., prebaseline) structural OCT illustrated the presence of intraretinal hyperreflective foci (HRF) at the site of type 3 neovascularization development in all patients. These foci were characterized by hyperfluorescence on dye angiography and by detectable flow on OCTA, identified with either the avascular slab (20%) or with both the deep retinal capillary plexus (DCP) and avascular slabs (80%). Typically, HRF with detectable flow on OCTA were characterized by the absence of intraretinal exudation (or very mild microcystic changes) until the lesion progressed from the DCP into the retinal pigment epithelium (RPE) and sub-RPE space. Of note, in 1 patient we observed the complete resolution of HRF despite the presence of OCTA flow and dye angiography hyperfluorescence detected at the preclinical stage examination. Conclusions Hyperreflective foci on structural OCT may represent early intraretinal neovascularization originating from the DCP, namely nascent type 3 neovascularization; these lesions can progress to active type 3 neovascularization or more rarely may regress without functional impairment. An advanced multimodal imaging approach is useful in detecting nascent type 3 lesions, which should be followed up carefully and treated as soon as possible if flow progresses to the RPE and sub-RPE space to prevent progression to late stages.

PURPOSE The concomitant use of triamcinolone acetonide (TA) at the completion of pars plana vitrectomy for the treatment of epiretinal membrane may speed up the anatomical and functional outcomes of surgery. We report the outcome of patients undergoing small-gauge vitrectomy for idiopathic epiretinal membrane peel with or without adjuvant TA therapy. DESIGN This is a retrospective, single-center case series. METHODS We included 75 eyes of 75 individual patients. Twenty-six patients (group A) had an adjuvant TA injection during surgery, whereas 49 patients (group B) were not injected. We assessed the patients for change in visual acuity (VA) and central macular thickness before and after surgery. RESULTS Group A had a mean logarithm of the minimum angle of resolution VA of 0.63 ± 0.33 and 0.51 ± 0.31 preoperatively and 3 months after surgery, respectively. Group B had a mean logarithm of the minimum angle of resolution VA of 0.47 ± 0.17 and 0.36 ± 0.17 preoperatively and 3 months after surgery, respectively. No significant difference was found between the groups in change of VA. The mean central macular thickness for groups A and B patients before surgery was 474.12 ± 120 μm and 445 ± 85 μm, decreasing to 369 ± 70 μm and 386 ± 60 μm at the final visit, respectively. The difference in macular thickness reduction between the groups was statistically significant. CONCLUSIONS Anatomical and functional improvement was found in both groups after surgery. Macular thickness was further reduced in the group of patients treated with adjuvant TA.

As rates of infectious syphilis continue to rise in the U.S., it is important to be familiar with known manifestations of ocular syphilis as well as report presentations not previously described in the literature. Here, the authors report a case of a 49-year-old myopic woman presenting with bilateral white dots characteristic of a white dot syndrome; these white dots were not evident on slit-lamp examination and became obvious on fundus autofluorescence. She tested positive and was successfully treated for syphilis. This case demonstrates that ocular syphilis can present with white dots and should be on the differential diagnosis of white dot syndromes. [ Ophthalmic Surg Lasers Imaging Retina. 2019;50:e52–e55.]

To report an unusual case of an elderly patient with transient outer retinal disruption resembling bilateral multiple evanescent white dot syndrome.Observational case report. Fundus photographs, fluorescein angiography, standard and ultra-widefield fundus autofluorescence, and cross-sectional and en face optical coherence tomography were used to characterize and describe the clinical findings.A 67-year-old woman presented with decreased vision and floaters in her left eye. Best-corrected visual acuity was 20/20-3 in the right eye and 20/80-2 in the left eye. Funduscopic examination showed small deep white dots and foveal granularity of the left eye corresponding to hyperautofluorescent spots on fundus autofluorescence and ellipsoid zone disruption on spectral domain optical coherence tomography. The asymptomatic right eye had evidence of subretinal deposits on spectral domain optical coherence tomography but was otherwise unremarkable. At 4-week follow-up, the patient noted resolution of her symptoms in the left eye but had developed floaters and blurry vision in her right eye. The left eye showed resolving white spots and ellipsoid zone disruption. However, the right eye had new evidence of white spots corresponding to hyperautofluorescent spots on fundus autofluorescence. Spectral domain optical coherence tomography demonstrated subretinal deposits overlying areas of ellipsoid zone disruption. At 8-week follow-up, the patient was asymptomatic in both eyes with best-corrected visual acuity of 20/20 in both eyes. The hyperautofluorescent spots on ultra-widefield fundus autofluorescence had faded with restoration of ellipsoid zone disruption in both eyes and disappearance of subretinal deposits.Our case demonstrates multimodal retinal imaging findings resembling multiple evanescent white dot syndrome in an elderly patient. The bilateral presentation, presence of subretinal deposits before symptom onset, and older age of the patient were atypical features for this entity.

Acute syphilitic posterior placoid chorioretinitis (ASPPC) is an uncommon manifestation of ocular syphilis with distinct clinical features. We describe new multimodal imaging findings in a patient with ASPPC.Observational case report with multimodal imaging.A 44-year-old woman presented with 5 days of decreased vision in her right eye. Visual acuity was counting fingers in her right eye and 20/20 in her left eye. Funduscopic examination of the right eye showed a yellow placoid macular lesion with extension beyond the equator, which was encircled by an annular ring of outer retinal whitening. Ultra-widefield fundus autofluorescence demonstrated hyperautofluorescence corresponding to the placoid lesion. Examination of the left eye appeared unremarkable, but ultra-widefield fundus autofluorescence showed an area of hyperautofluorescence located superonasal to the optic nerve. Optical coherence tomography of the right eye demonstrated subretinal fluid and overlying disruption of the ellipsoid zone. Fluorescein angiography demonstrated early hypofluorescent and hyperfluorescent spots and late staining within the placoid lesion. Optical coherence tomography angiography showed several areas of decreased flow signal within the placoid lesion at the level of the choriocapillaris. Laboratory testing revealed a rapid plasma reagin titer of 1:1,024. Two months after treatment with intravenous penicillin G, visual acuity had improved to 20/25 in her right eye, and optical coherence tomography showed partial restoration of the ellipsoid zone. The annular ring resolved with near normalization of fundus autofluorescence and optical coherence tomography angiography demonstrated resolution of flow.Multimodal imaging provides further insight into the pathogenesis of ASPPC. Ultra-widefield fundus autofluorescence may show evidence of ellipsoid zone disruption in areas that clinically appear normal. Flow voids within the choriocapillaris in ASPPC appear to resolve with appropriate treatment, a finding that suggests a transient disruption of choriocapillaris flow in ASPPC.

To define the range and life cycles of cuticular drusen phenotypes using multimodal imaging and to review the histologic characteristics of cuticular drusen.Retrospective, observational cohort study and experimental laboratory study.Two hundred forty eyes of 120 clinic patients with a cuticular drusen phenotype and 4 human donor eyes with cuticular drusen (n = 2), soft drusen (n = 1), and hard drusen (n = 1).We performed a retrospective review of clinical and multimodal imaging data of patients with a cuticular drusen phenotype. Patients had undergone imaging with various combinations of color photography, fluorescein angiography, indocyanine green angiography, near-infrared reflectance, fundus autofluorescence, high-resolution OCT, and ultrawide-field imaging. Human donor eyes underwent processing for high-resolution light and electron microscopy.Appearance of cuticular drusen in multimodal imaging and the topography of a cuticular drusen distribution; age-dependent variations in cuticular drusen phenotypes, including the occurrence of retinal pigment epithelium (RPE) abnormalities, choroidal neovascularization, acquired vitelliform lesions (AVLs), and geographic atrophy (GA); and ultrastructural and staining characteristics of druse subtypes.The mean age of patients at the first visit was 57.9±13.4 years. Drusen and RPE changes were seen in the peripheral retina, anterior to the vortex veins, in 21.8% of eyes. Of eyes with more than 5 years of follow-up, cuticular drusen disappeared from view in 58.3% of eyes, drusen coalescence was seen in 70.8% of eyes, and new RPE pigmentary changes developed in 56.2% of eyes. Retinal pigment epithelium abnormalities, AVLs, neovascularization, and GA occurred at a frequency of 47.5%, 24.2%, 12.5%, and 25%, respectively, and were significantly more common in patients older than 60 years of age (all P0.015). Occurrence of GA and neovascularization were important determinants of final visual acuity in eyes with the cuticular drusen phenotype (both P 0.015). Small cuticular drusen typically demonstrated a homogenous ultrastructural appearance similar to hard drusen, whereas fragmentation of the central and basal contents was seen frequently in larger cuticular drusen.Although the ultrastructural characteristics of cuticular drusen appear more similar to those of hard drusen, their lifecycle and macular complications are more comparable with those of soft drusen. Cuticular drusen phenotype may confer a unique risk for the development of GA and neovascularization.