EVALUATING ULTRA-WIDEFIELD IMAGING UTILITY IN THE DETECTION OF TREATMENT-REQUIRING PERIPHERAL RETINAL TEARS AND HOLES.

PURPOSE: To determine the utility of ultra-widefield (UWF) imaging in detecting pathologic peripheral retinal tears and holes. METHODS: This was a retrospective, observational study. One-hundred ninety-eight eyes of 198 patients diagnosed with acute posterior vitreous detachment were included. Eyes were divided into two groups: 89 eyes with peripheral retinal holes and tears treated with laser retinopexy (treatment group) and 109 control eyes. Patients underwent UWF imaging and indirect ophthalmoscopy with scleral depression. UWF images from both groups were reviewed by two blinded graders and then compared with funduscopic examination and medical records. RESULTS: UWF imaging identified 60 of the 89 eyes (sensitivity of 67.4%) found to have treatment-requiring peripheral retinal lesions and 107 of the 109 control eyes (specificity of 98.2%).The distribution of misses based on octant location did reach statistical significance ( P = 0.004). Lesions anterior to the equator were more likely to be missed (21/41 eyes, 51.2%) compared with those located posterior to the equator (4/20 eyes, 25.0%) and at the equator (4/28, 14.3%), P = 0.002. The combined discordance rate between graders in the entire cohort was 12.1% (24/198 eyes) yielding an interrater agreement of 87.9%. CONCLUSION: UWF imaging showed a moderate sensitivity and high specificity in detecting treatment-requiring retinal tears and holes, with high interrater agreement. Given there is only a moderate sensitivity in identifying treatment-requiring retinal tears and holes, UWF imaging can assist with clinical examination, but a 360-degree scleral depressed examination should remain the gold standard.

ROLE OF OPTICAL COHERENCE TOMOGRAPHY FOR PREDICTING POSTOPERATIVE VISUAL OUTCOMES AFTER REPAIR OF MACULA-OFF RHEGMATOGENOUS RETINAL DETACHMENT.

PURPOSE: To identify any prognostic associations between preoperative optical coherence tomography findings and postoperative visual outcomes in patients with macula-off rhegmatogenous retinal detachment. METHODS: A retrospective, single-center study of patients diagnosed with macula-off rhegmatogenous retinal detachment whom underwent surgical reattachment from 2012 to 2017. Optical coherence tomography images were analyzed by two retina surgeons. Outcome measures included "good" final vision (best-corrected visual acuity of 20/40 or better), "poor" final vision (best-corrected visual acuity of 20/200 or worse), and change in vision (worsened, improved, and improved ≥15 letters) at most recent follow-up. P values were calculated using t tests, analysis of variance, Wilcoxon rank-sum, or Kruskall-Wallis test. RESULTS: A total of 49 eyes were included. There was a significant difference in the mean preoperative central retinal thickness between patients who had good final vision and patients who did not (96 µm vs. 161 µm, P = 0.048). In addition, a worse preoperative best-corrected visual acuity and greater subretinal fluid height were associated with vision improvement (P < 0.001). Those with persistent ellipsoid zone disruption postoperatively were less likely to have good final vision (odds ratio = 0.217, 95% confidence interval: 0.057-0.828). CONCLUSION: A lower mean preoperative central retinal thickness is associated with good visual prognosis. Eyes with ellipsoid zone disruption postoperatively were less likely to have good final vision. Future studies should include a larger cohort of patients and more optical coherence tomography variables to address the inconsistencies in the current literature.

SPECTRAL DOMAIN OPTICAL COHERENCE TOMOGRAPHY FINDINGS IN COATS DISEASE.

PURPOSE: To evaluate microstructural retinal abnormalities on spectral domain optical coherence tomography (SD-OCT) imaging of eyes with Coats disease. METHODS: This is a multicenter, retrospective study in which SD-OCT images of patients with treatment-naive Coats disease were correlated with clinical examination and visual acuity and, when available, followed longitudinally over time. RESULTS: Macular SD-OCT of 27 eyes with Coats disease revealed intraretinal edema (59%), intraretinal exudates (67%), subretinal fluid (37%), subretinal exudate (48%), ellipsoid zone disruption (52%), external limiting membrane disruption (41%), and subfoveal nodule (26%). All these microstructural abnormalities correlated with worse baseline and final visual acuities (P < 0.05) on univariate analysis, except for intraretinal edema which exhibited a nonstatistically significant trend toward worse baseline visual acuity (P = 0.16). Within stage 2b eyes, external limiting membrane disruption and subretinal nodule on SD-OCT were associated with worse baseline visual acuity (P = 0.02 for both), and there was a trend toward worse final visual acuity with external limiting membrane disruption and subretinal nodule (P = 0.17 for both) and worse baseline (P = 0.08) and final (P = 0.13) visual acuities with ellipsoid zone disruption. No microstructural abnormalities were noted on OCT of fellow eyes. CONCLUSION: Spectral domain OCT can identify microstructural abnormalities in Coats disease that are associated on univariate analysis with worse baseline visual acuity and visual prognosis. Further larger studies are necessary.

SPECTRAL DOMAIN OPTICAL COHERENCE TOMOGRAPHY FINDINGS IN MACULA-INVOLVING CYTOMEGALOVIRUS RETINITIS.

PURPOSE: To evaluate the microstructural features of cytomegalovirus (CMV) retinitis by spectral domain optical coherence tomography (OCT). METHODS: Subjects were patients with macula-involving CMV retinitis with OCT imaging. The leading edge of retinitis in the macula was identified based on fundus imaging, and OCT findings were longitudinally evaluated in three areas: within the area of active retinitis, at the leading edge of retinitis, and just beyond the leading edge of retinitis. RESULTS: Optical coherence tomography imaging of macular CMV retinitis identified vitreous cells in 10 eyes (100%), posterior vitreous detachment in four eyes (40%), broad-based vitreomacular traction in one eye (10%), epiretinal membrane in eight eyes (80%), and lamellar hole-associated epiretinal proliferation associated with an atrophic hole in one eye (10%). Retinal architectural disruption, disruption of inner retinal layers, disruption of the external limiting membrane, and ellipsoid zone abnormalities were noted within the area of retinitis in all eyes and decreased in frequency and severity at and beyond the leading edge of retinitis, although all 10 eyes (100%) exhibited one of these abnormalities, especially outer retinal microabnormalities, beyond the leading edge of retinitis. CONCLUSION: Microstructural abnormalities were frequently noted on OCT of CMV retinitis, including within the retina beyond the leading edge of retinitis identified by corresponding fundus imaging. Outer retinal abnormalities were noted more frequently than inner retinal abnormalities beyond the leading edge of retinitis. These findings provide insight into the effects of CMV retinitis on retinal microstructure and potentially on vision and highlight the potential utility of OCT for monitoring microprogression of macula-involving CMV retinitis.

ULTRA-WIDEFIELD IMAGING OF POSTERIOR SEGMENT PATHOLOGY IN THE SETTING OF THE BOSTON KERATOPROSTHESIS.

PURPOSE: To evaluate the ability to visualize and document posterior segment pathology through the Boston keratoprosthesis (KPro) using the Optos P200Tx ultra-widefield (UWF) scanning laser ophthalmoscope. METHODS: A retrospective chart review was conducted of patients who underwent Boston Type I keratoprosthesis implantation and who subsequently were imaged with an UWF system. Ultra-widefield images were reviewed to evaluate for vitreoretinal pathology and were compared with the clinical examination. RESULTS: In this series of 10 patients (10 eyes), 100% of vitreoretinal pathology found on clinical examination was detectable using the Optos system. In 4 cases (40%), UWF imaging provided superior detection of pathology compared with the clinical examination by imaging through retroprosthetic membranes (3 cases) and by detection of a retinal detachment (one case). In 1 case (10%), B-scan ultrasonography was needed to characterize vitreoretinal pathology that could not be definitively distinguished on UWF imaging and was difficult to detect on clinical examination. Ultra-widefield imaging detected the following vitreoretinal pathologies in KPro eyes: retinal hemorrhage, epiretinal membrane, retinal detachment, proliferative diabetic retinopathy, and choroidal folds. CONCLUSION: Ultra-widefield imaging provides a high-resolution view of the posterior pole and periphery despite the limitations of imaging through the narrow optic of Boston Type I keratoprosthesis, and it may improve visualization through retroprosthetic membranes. Detection and documentation of vitreoretinal complications in the setting of a permanent keratoprosthesis may be enhanced using UWF imaging.

A comparison of same setting versus delayed vitrectomy in the management of retained lens fragments after cataract surgery.

PURPOSE: Intravitreal retained lens fragments are a rare but potentially serious complication of phacoemulsification. The purpose of this study was to compare same setting ("no wait") vitrectomy with delayed surgery in the management of retained lens fragments in a single academic setting. METHODS: This study is a retrospective nonrandomized study of all patients undergoing pars plana vitrectomy for retained lens fragments after cataract surgery from 2007 to 2012. Outcomes included visual acuity and the development of various complications such as retinal detachment, elevated intraocular pressure >30 mmHg, and cystoid macular edema. Multivariate analysis was performed to adjust for potentially confounding variables such as age and preoperative visual acuity. RESULTS: Twenty-eight consecutive eyes (13 same setting, 15 delayed setting) were included in the analysis. Patients in the same setting group were older than in the delayed group (81.00 vs. 72.87 years, P = 0.053). No other preoperative differences existed between the groups (axial length, preoperative vision, and intraocular pressure). The mean time to pars plana vitrectomy in the delayed group was 26.6 days (range, 1-91 days). The mean follow-up time was 363 days (same setting) and 643 days (delayed). At the most recent follow-up, no significant difference existed in mean vision between the same setting (logMAR, 0.42) and the delayed group (logMAR, 0.57) (P = 0.132). Multivariate analysis showed no difference in final vision when adjusting for age and preoperative vision. Although there was a trend for eyes in the same setting group to obtain good vision (≥ 20/40) faster, a higher percentage of eyes in the delayed group obtained good vision at the most recent follow-up (66.7 vs. 23.1%, P = 0.02). More eyes in the delayed group had an intraocular pressure >30 at any point (P = 0.055). There was no significant difference between the groups in any other complications such as retinal detachment, choroidal detachment, and cystoid macular edema during the follow-up. CONCLUSION: In this cohort, same setting pars plana vitrectomy offers no significant visual acuity advantage over delayed pars plana vitrectomy in patients with retained lens fragments. Fewer eyes in the same setting group "ever" had an intraocular pressure ≥ 30 during follow-up, whereas no other complication differences were seen between the groups.

Pars plana vitrectomy compared with pars plana vitrectomy combined with scleral buckle in the primary management of noncomplex rhegmatogenous retinal detachment.

PURPOSE: To compare pars plana vitrectomy (PPV) with PPV combined with scleral buckle (PPV/SB) in the treatment of primary, noncomplex rhegmatogenous retinal detachment in an academic setting. METHODS: Retrospective review of 74 consecutive cases that underwent either PPV or PPV/SB for primary rhegmatogenous retinal detachment at New York Presbyterian Hospital, Weill Cornell Medical College. Fifty-two eyes underwent PPV alone while 22 eyes had PPV combined with SB. All eyes had a minimum of 2 months of follow-up. The main outcome measure was single surgery anatomical success. RESULTS: Patients in the PPV/SB group were less likely to be phakic (P = 0.05) and more likely to have an inferior retinal break (P = 0.001) when compared with the PPV group. Between groups, there was no difference in eyes with peripheral retinal lattice degeneration (P = 0.929), multiple breaks (P = 0.801), breaks seen preoperatively (P = 0.095), or those presenting with the macula off retinal detachment (P = 0.548). The majority of patients in both groups underwent small-gauge surgery (23 G or 25 G) (P = 0.65). Attachment of the retina was obtained in 100% of the patients in both groups at most recent follow-up. Single surgery anatomical success was similar between groups (83% PPV vs. 86% PPV/SB; P = 0.695). Mean best-corrected Snellen visual acuity improved in both groups (P = 0.75), with a final best-corrected Snellen visual acuity of 0.418 logMAR in the PPV group and 0.479 logMAR in the PPV/SB group (P = 0.61). When comparing PPV with PPV/SB, no difference in single surgery anatomical success existed after evaluating eyes with inferior breaks (P = 0.68), pseudophakia (P = 0.75), or when small-gauge surgery was performed (P = 0.76). CONCLUSION: We did not find significant differences in single surgery anatomical success, final anatomical success, or change in visual acuity when comparing PPV with PPV/SB in the repair of primary noncomplex rhegmatogenous retinal detachment in an academic setting where vitreoretinal fellows participate in key aspects of all cases.

Implementation of a Teleophthalmology Screening Program for Diabetic Retinopathy in New York City.

Purpose: To examine the implementation of a teleophthalmology program for diabetic retinopathy (DR) screening at a metropolitan hospital system and identify the challenges that the clinical teams encountered using the program. Methods: The study was conducted in 2 parts. The first was a pilot retrospective chart review of 300 consecutive patients screened for DR by the teleophthalmology screening program. The baseline variables, DR capture rate and staging, and continuity of care for those diagnosed with DR were analyzed. The second was a web-based survey identifying the barriers encountered by 36 physicians and clinical staff as they participated in the teleophthalmology screening program. Results: Part 1: Of the patients evaluated, 57 (19.0%) were diagnosed with DR; 42 (73.7%) had mild nonproliferative DR (NPDR), 7 (12.3%) had moderate NPDR, none had severe NPDR, and 8 (14.0%) had PDR. Thirty-one patients (54.4%) with retinopathy diagnoses were referred for an in-person follow-up at the clinic while the rest continued monitoring via the program. Of this subset, 22 (71.0%) completed the follow-up visit. Part 2: The survey respondents comprised 28 physicians (77.8%), 6 licensed nurse practitioners (16.7%), and 2 medical assistants (5.6%). Twenty-two providers (71.0%) preferred initiating referrals for in-person annual examinations over teleophthalmology screening referrals. The most common barriers described were related to workflow interruption, time constraints, and staff shortages. Conclusions: The teleophthalmology DR screening program allowed identification of early or absent DR at clinics in an urban setting (New York City). The findings suggest areas for targeted improvement in the screening program to better complement internal referral practices' workflows.

Google Search Trends to Assess Public Interest and Concern About Pegcetacoplan for the Treatment of Geographic Atrophy.

OBJECTIVE: To assess global trends in interest surrounding the newly Food and Drug Administration (FDA)-approved treatment for geographic atrophy, (GA), Syfovre (pegcetacoplan), and related searches. METHODS: We utilized Google Trends, in order to gauge the public interest in Syfovre from October 16, 2022, to October 8, 2023. RESULTS: Notable spikes in relative search volumes (RSV)s for "Syfovre" were observed in mid-to-late February 2023, and in March and April 2023, coinciding with the drug's FDA approval and introduction to the market. Of the various side effects, retinal vasculitis garnered the most significant attention, with a sharp rise in RSV in mid-July 2023. Geographic variation was evident, with the highest RSVs for "Syfovre" originating from users on the East Coast. CONCLUSION: Google Trends proves to be a useful tool for gaining insight into public interest in pegcetacoplan as a treatment for GA. [Ophthalmic Surg Lasers Imaging Retina 2024;55:452-460.].

Incidence of Blepharoptosis Following Intravitreal Anti-Vascular Endothelial Growth Factor Injections.

PURPOSE: To determine the incidence of blepharoptosis after intravitreal anti-vascular endothelial growth factor (anti-VEGF) injections and compare the rates of blepharoptosis between patients injected with an eyelid speculum and those injected without a speculum. DESIGN: Retrospective cohort study. METHODS: International Classification of Diseases, Tenth Revision (ICD-10), codes were used to identify patients with exudative age-related macular degeneration (AMD) and those who developed ptosis after intravitreal injections. Patients with nonexudative AMD who did not receive intravitreal injections served as controls. The outcomes were the incidence of ptosis in the injection group compared to the noninjection group and incidence of ptosis in patients whose injections were performed with an eyelid speculum as compared to those whose injections were performed without a speculum. RESULTS: We recruited 1100 exudative AMD patients who received at least 1 intravitreal anti-VEGF injection and 2258 nonexudative AMD patients who had not received an injection. In the injection group, 18 of 1100 patients (1.6%) developed ptosis, compared with 52 of 2258 patients (2.3%) in the noninjection group (P = .25). Within the injection group, ptosis was mostly bilateral, diagnosed on average 22.4 months after the initial injection, and after more than a 1-year injection-free period. Eleven of 537 patients (2.0%) injected without a speculum developed ptosis, compared with 8 of 444 patients (1.8%) injected with a speculum (P = .82). CONCLUSIONS: No statistically significant differences in incidence rates of ptosis were observed. In this analysis, neither intravitreal anti-VEGF injections nor speculum use during injections appears to increase the risk of ptosis.

Adverse Events Associated With 3 Vitrectomy Platforms Reported to the US FDA MAUDE Database.

Purpose: To identify and describe adverse events (AEs) observed with real-world use of the following 3 vitrectomy platforms: Constellation (Alcon), Enhancing Visual Acuity (EVA, Dutch Ophthalmic Research Center), and Stellaris (Bausch + Lomb). Methods: All reports submitted to the US Food and Drug Administration's Manufacturer and User Facility Device Experience (MAUDE) database between January 2010 and November 2021 that were associated with the 3 vitrectomy platforms were analyzed. Each report was reviewed for AEs or consequences and the type of complication noted. Duplicates and reports with an inadequate narrative to categorize the event were excluded. A descriptive analysis was performed for the prevalence of device-specific issues within each platform. Results: The analysis included 2534 reports (1738 Constellation, 117 EVA, 679 Stellaris). Overall, the most commonly reported complications involved the vitrectomy probe (n = 957 [37.8%]) and the central processing unit (n = 368 [14.5%]). Differences in the distribution of AEs among the platforms were noted, with vitrectomy probe issues being the most reported events for the Constellation and Stellaris and infusion issues for the EVA. Infusion issues most frequently led to reports of patient harm with the Constellation (31/1738 [1.8%]) and EVA (7/116 [6.0%]), while issues with the vitrectomy probe were reported with the Stellaris (11/679 [1.6%]). Conclusions: An analysis of real-world data in the MAUDE database highlighted the spectrum of device-specific AEs of greatest relevance to surgical practice. Familiarity with potential device complications will help minimize harm to patients.

Disparities Between Clinical Trial Recruitment and Real-World Demographics in Macular Edema Secondary to Retinal Vein Occlusion.

PURPOSE: Clinical trial cohorts frequently differ demographically from the overall population receiving treatment for the condition under study. Our study describes the racial, ethnic, and gender composition of the cohorts of retinal vein occlusion (RVO) macular edema (ME) clinical trials and compares this to the racial, ethnic, and gender composition of patients undergoing treatment for ME secondary to RVO from the (Intelligent Research in Sight) IRIS® Registry. DESIGN: Retrospective observational case series Subjects: Participants in RVO-ME clinical trials that met the following inclusion criteria: conducted in the United States of America, Phase III completed, data reported between Jan 1, 2000, and Jan 1, 2020, and demographic information reported with results. METHODS: This study identified clinical trials by searching PubMed with the following search terms; "retinal vein occlusion" and "clinical trial" and by searching ClinicalTrials.gov with the search term "retinal vein occlusion". MAIN OUTCOME MEASURES: The primary outcome was the enrollment fraction defined as the number of trial enrollees divided by the reference sample size of RVO patients undergoing treatment for ME from published IRIS® Registry (Intelligent Research in Sight) data. Enrollment fraction was compared between different races, ethnicities, and genders. RESULTS: Eight clinical trials met our inclusion criteria. Compared to the enrollment fraction of 7.69% among Whites, lower enrollment fractions were found in Black patients (4.32%, odds ratio [OR] 0.541, confidence interval [CI] 0.468-0.626, P< 0.001) and Hispanic patients (3.38%, OR 0.420, CI 0.351-0.503, P<0.001), and higher enrollment fraction in Asian patients (10.68%, OR 1.436, CI 1.207-1.708, P<0.001). Men were more likely to enroll in the clinical trials compared to women (enrollment fraction, 7.69% vs 5.77%, respectively, OR 1.364, CI 1.273-1.462, P < 0.001). CONCLUSIONS: RVO-ME clinical trials have a higher relative proportion of Asian, White and male subjects when compared to the population undergoing treatment for ME secondary to RVO. Further efforts should encourage clinical trial recruitment that is reflective of the RVO population undergoing treatment for ME to ensure generalizability of clinical trial results.

Anti-VEGF Pharmaceutical Prior Authorization in Retina Practices.

Importance: Anti-vascular endothelial growth factor (VEGF) intravitreal injections, a mainstay of treatment for many retinal diseases to optimize visual outcomes, have been included in prior authorization (PA) initiatives. However, if clinicians are extremely accurate in their use of anti-VEGF medications, such administrative burdens may need reconsideration. Objective: To quantify PA for anti-VEGF medications (aflibercept, ranibizumab, and bevacizumab) that were approved and determine associated administrative burdens experienced by retina practices. Design, Setting, and Participants: Prospective multicenter quality improvement study conducted from January 2022 through June 2022, and participants were 9 private retina practices across the US. Main Outcomes and Measures: Overall rate of approval of PA requests, reasons for requesting PA, and overall rate of delay of care resulting from PA procedures. Results: In total, 2365 PA requests were recorded, 2225 of which met inclusion criteria. Overall, 2140 (96.2%) requests were approved. The most common reason for requesting PA, at 64% (1423 of 2225 requests), was reauthorization for a previously utilized medication. Of the 2140 approvals, 59.6% (1277) resulted in a delay in care greater than 24 hours, and 40% (863) were given on the date of service. In a granular analysis of a subset of delayed approvals, 23.9% (173 of 725) were approved within 1 day, 15.9% (115 of 725) were approved within 2 to 3 days, 21.5% (156 of 725) were approved within 4 to 7 days, 26.3% (191 of 725) were approved within 8 to 31 days, and 12.4% (90 of 725) were approved within more than 31 days. Overall, PA denial for step therapy was 2.9% (65 of 2225) of requests and uncovered diagnoses was 0.9% (20 of 2225) of requests. The median staff time spent to obtain a single PA was 100 (range, 0-200) minutes. Conclusions and Relevance: In this study, PA requests were almost always approved but led to a delay in patient care in most patients. The current study suggests that the PA process may not be effective for retina specialists if these results can be generalized to other practices in the US and if less burdensome and less costly approaches could result in similar approval rates. Potential short-term solutions may include eliminating the PA process for bevacizumab and reauthorizations for established patients.

The use of digital imaging in the identification of skip areas after laser treatment for retinopathy of prematurity and its implications for education and patient care.

PURPOSE: To describe the utility of using wide-angle digital imaging in the training for retinopathy of prematurity with laser and in identifying common locations of skip areas that were present after initial panretinal photocoagulation with indirect ophthalmoscopy by ophthalmologists-in-training. METHODS: Retrospective review of digital retinal images of 22 eyes of 12 infants who had undergone laser treatment for retinopathy of prematurity performed by ophthalmologists-in-training. Presence of skip areas was determined by masked review of photographs. The location of skip areas was classified based on two axes: 1) circumferential (in one of six clock-hour regions) and 2) radial (adjacent to the retinal ridge, adjacent to the ora serrata, or isolated patches of greater than one laser burn width). RESULTS: A total of 30 skip areas were identified in the 22 eyes treated with laser photocoagulation. Based on the circumferential location, a significant difference in skip area distribution was found (P = 0.02). Regions with the highest percentage of skip areas were between the clock hours 11:00 to 1:00 (45%) and 5:00 to 7:00 (41%). Based on the radial location, 40% of all skip areas were found near the ora serrata, 17% near the ridge, and 43% as isolated patches (P = 0.14). CONCLUSION: Skip areas after indirect panretinal laser photocoagulation by ophthalmologists-in-training were easily visualized by wide-angle digital imaging, after being missed by the trainee during the initial treatment procedure. Most skip areas in this study occurred in the superior or inferior retina. Digital imaging can assist ophthalmologists in visualizing all regions of the retina, can identify inadequate areas of laser treatment, and may reduce the need for retreatment after initial laser for retinopathy of prematurity.

Genetic variants near TIMP3 and high-density lipoprotein-associated loci influence susceptibility to age-related macular degeneration.

We executed a genome-wide association scan for age-related macular degeneration (AMD) in 2,157 cases and 1,150 controls. Our results validate AMD susceptibility loci near CFH (P < 10(-75)), ARMS2 (P < 10(-59)), C2/CFB (P < 10(-20)), C3 (P < 10(-9)), and CFI (P < 10(-6)). We compared our top findings with the Tufts/Massachusetts General Hospital genome-wide association study of advanced AMD (821 cases, 1,709 controls) and genotyped 30 promising markers in additional individuals (up to 7,749 cases and 4,625 controls). With these data, we identified a susceptibility locus near TIMP3 (overall P = 1.1 x 10(-11)), a metalloproteinase involved in degradation of the extracellular matrix and previously implicated in early-onset maculopathy. In addition, our data revealed strong association signals with alleles at two loci (LIPC, P = 1.3 x 10(-7); CETP, P = 7.4 x 10(-7)) that were previously associated with high-density lipoprotein cholesterol (HDL-c) levels in blood. Consistent with the hypothesis that HDL metabolism is associated with AMD pathogenesis, we also observed association with AMD of HDL-c-associated alleles near LPL (P = 3.0 x 10(-3)) and ABCA1 (P = 5.6 x 10(-4)). Multilocus analysis including all susceptibility loci showed that 329 of 331 individuals (99%) with the highest-risk genotypes were cases, and 85% of these had advanced AMD. Our studies extend the catalog of AMD associated loci, help identify individuals at high risk of disease, and provide clues about underlying cellular pathways that should eventually lead to new therapies.

Primary and secondary focal choroidal excavation morphologic phenotypes, associated ocular disorders and prognostic implications.

AIMS: To characterise and classify the morphological, clinical and tomographic characteristics of focal choroidal excavation (FCE) lesions to determine their prognostic implications. METHODS: 36 eyes with FCE (32 patients) underwent multimodal imaging, including spectral domain optical coherence tomography and fundus autofluorescence. FCE lesions were classified into three subtypes: (1) type 1: myopic (central choroidal thickness: <100 µm), (2) type 2: suspected congenital (central choroidal thickness: 100-200 µm, without associated chorioretinal pathology) and (3) type 3: secondary or acquired (central choroidal thickness: >200 µm, with associated chorioretinal pathology). RESULTS: 80.6% of eyes were followed longitudinally (26.8±18.8 months). There were 9 type 1 FCEs (myopic), 8 type 2 FCEs (U-shaped, congenital) and 19 type 3 FCEs (V-shaped, secondary). Type 2 FCEs trended towards larger maximum widths (p=0.0563). Type 3 FCEs were associated with central serous chorioretinopathy or pachyvessels (47.4%), but were also seen in pattern dystrophy, geographic atrophy, inactive choroiditis, torpedo maculopathy and adult-onset vitelliform dystrophy. Choroidal neovascular membranes (CNVMs) were more prevalent in type 3 FCE (41.2% compared with 11.1% for type 1 FCE, p=0.251, and 0% for type 2 FCE, p=0.043). CONCLUSIONS: The FCE types, stratified by central choroidal thickness, demonstrated distinct morphological characteristics and associated findings. The classification scheme held prognostic implications as type 3 FCE with V shapes were associated with other chorioretinal conditions and were more likely to develop CNVM.

Association between high-risk disease loci and response to anti-vascular endothelial growth factor treatment for wet age-related macular degeneration.

PURPOSE: To investigate whether there is an association between known age-related macular degeneration genetic risk variants in the CFH, ARMS2, and HTRA1 genes and response to anti-vascular endothelial growth factor (VEGF) (ranibizumab or bevacizumab) treatment for wet age-related macular degeneration. METHODS: A retrospective review of 150 patients with documented wet age-related macular degeneration based on clinical examination and fluorescein angiogram was performed. Patients received anti-VEGF therapy with ranibizumab and/or bevacizumab. Patients were genotyped for the single-nucleotide polymorphism rs1061170, rs10490924, rs3750848, rs3793917, rs11200638, and rs932275 and for the indel del443ins54 spanning the CFH, ARMS2, and HTRA1 genes. RESULTS: There were 57 patients who were characterized as negative responders to anti-VEGF therapy, and 93 patients who were characterized as positive responders. There was no significant difference in mean baseline visual acuity between the groups. Negative responders were followed for a mean duration of 24.0 months, while positive responders were followed for a mean duration of 22.0 months. Although the frequency of the at-risk alleles was higher in the positive responders when compared with the negative responder, this did not reach statistical significance. Additionally, there was no significant association between genotype and the number of injections or absolute change in visual acuity in both groups of responders. CONCLUSION: In our patient cohort, there was no statistically significant association between response to anti-VEGF therapy and the genotype in both positive-responder and negative-responder groups. Larger studies with more power are necessary to further determine whether a pharmacogenetic association exists between wet age-related macular degeneration and anti-VEGF therapy.

Multilayered macular hemorrhages as an unusual complication of transorbital neuroendoscopic surgery.

Purpose: To report a case of multilayered intraocular hemorrhage at the posterior pole as a complication of transorbital neuroendoscopic surgery. Observations: Our patient underwent an uncomplicated endoscopic transorbital resection of a left sphenoid wing meningioma. In the immediate post-operative period, the patient reported blurred vision of her left eye, and dilated fundus examination demonstrated multilayered hemorrhages at the posterior pole. No intracranial hemorrhage was identified on post-operative imaging. Due to persistent subnormal visual acuity and non-clearing hemorrhage over several weeks of follow-up, a pars plana vitrectomy with peeling of the internal limiting membrane was performed to clear the hemorrhagic component obscuring the macula. Conclusions and Importance: We report the first case of multilayered intraocular hemorrhages at the posterior pole, mimicking Terson syndrome, in the absence of intracranial hemorrhage or elevated intracranial pressure as a complication of transorbital surgery.

The Prevalence of Retinal Disease and Associated CNS Disease in Young Patients with Incontinentia Pigmenti.

PURPOSE: To evaluate the prevalence of retinal disease on fluorescein angiography (FA) in patients with incontinentia pigmenti (IP) and to compare the severity of retinal disease in those with and without known central nervous system (CNS) disease. DESIGN: Multi-institutional consecutive retrospective case series. SUBJECTS: New patients with a diagnosis of IP were seen at the Casey Eye Institute at the Oregon Health and Science University (OHSU), Moran Eye Center, University of Utah, or Bascom Palmer Eye Institute, University of Miami from December 2011 to September 2018. METHODS: Detailed ophthalmoscopic examination and FA were recommended for all new patients and performed on every patient who had parental consent. Ophthalmoscopic findings and FA images were graded for severity by 2 masked graders on a 3-point scale: 0 = no disease, 1 = vascular abnormalities without leakage, 2 = leakage or neovascularization, and 3 = retinal detachment. The presence of known CNS disease was documented. Additional cases were obtained from a pediatric retina listserv for examples of phenotypic variation. MAIN OUTCOME MEASURES: The proportion of eyes noted to have disease on ophthalmoscopy compared with FA and the severity of retinal disease in those with and without known CNS disease. RESULTS: Retinal pathology was detected in 18 of 35 patients (51%) by indirect ophthalmoscopy and 26 of 35 patients (74%) by FA (P = 0.048) in a predominantly pediatric population (median age, 9 months). Ten patients (29%) had known CNS disease at the time of the eye examination. A Wilcoxon rank-sum test indicated that the retinal severity scores for patients with CNS disease (median, 2) were significantly higher than the retinal severity scores for patients without CNS disease (median, 1), z = -2.12, P = 0.034. CONCLUSIONS: Retinal disease is present in the majority of patients with IP, and ophthalmoscopic examination is less sensitive than FA for detection of disease. There may be a correlation between the severity of retinal and CNS disease.

Evidence of association of APOE with age-related macular degeneration: a pooled analysis of 15 studies.

Age-related macular degeneration (AMD) is the most common cause of incurable visual impairment in high-income countries. Previous studies report inconsistent associations between AMD and apolipoprotein E (APOE), a lipid transport protein involved in low-density cholesterol modulation. Potential interaction between APOE and sex, and smoking status has been reported. We present a pooled analysis (n = 21,160) demonstrating associations between late AMD and APOε4 (odds ratio [OR] = 0.72 per haplotype; confidence interval [CI]: 0.65-0.74; P = 4.41×10(-11) ) and APOε2 (OR = 1.83 for homozygote carriers; CI: 1.04-3.23; P = 0.04), following adjustment for age group and sex within each study and smoking status. No evidence of interaction between APOE and sex or smoking was found. Ever smokers had significant increased risk relative to never smokers for both neovascular (OR = 1.54; CI: 1.38-1.72; P = 2.8×10(-15) ) and atrophic (OR = 1.38; CI: 1.18-1.61; P = 3.37×10(-5) ) AMD but not early AMD (OR = 0.94; CI: 0.86-1.03; P = 0.16), implicating smoking as a major contributing factor to disease progression from early signs to the visually disabling late forms. Extended haplotype analysis incorporating rs405509 did not identify additional risks beyond ε2 and ε4 haplotypes. Our expanded analysis substantially improves our understanding of the association between the APOE locus and AMD. It further provides evidence supporting the role of cholesterol modulation, and low-density cholesterol specifically, in AMD disease etiology.