Association of Cutaneous Keloids, Hypertrophic Scarring, and Fibrosis with Risk of Postoperative Proliferative Vitreoretinopathy.

PURPOSE: To assess an association between cutaneous keloids, hypertrophic scarring, and fibrosis (KHF) and risk of postoperative proliferative vitreoretinopathy (PVR) after rhegmatogenous retinal detachment (RRD) repair. DESIGN: Retrospective, population-based cohort study. PARTICIPANTS: Patients aged ≥ 18 years who underwent initial retinal detachment (RD) repair with pars plana vitrectomy with or without scleral buckle (SB) (Current Procedural Terminology [CPT] 67108), pneumatic retinopexy (67110), and primary SB (67107) from January 1, 2003, to March 1, 2023. METHODS: A de-identified electronic health record database through TriNetX, a global health research network, was used to analyze patients. Patients were queried for International Classification of Diseases, 10th Revision (ICD-10) codes L91.0 (hypertrophic scar) and L90.5 (scar conditions and fibrosis of skin). Frequency of subsequent diagnosis of PVR (H35.2) and CPT codes for secondary surgery including complex RD repair (67113) were determined. Patients with proliferative diabetic retinopathy (PDR) (ICD-10 H10.35/H11.35) were excluded. Descriptive statistics (Z-test) and propensity score matching (PSM) were used to match for age, sex, and race. MAIN OUTCOME MEASURES: Prevalence of H35.2 and CPT 67113 within 180 days after RRD repair in the KHF cohort versus the non-KHF cohort. RESULTS: Among patients with CPT 67108, 1061 in each cohort (KHF and non-KHF) were analyzed after PSM. The mean (standard deviation) age was 60.7 (15.2) years. Within 180 days, 10.1% of patients in the KHF cohort and 3.4% in the non-KHF cohort had a diagnosis of PVR (H35.2) (P < 0.001, odds ratio [OR], 3.2; 95% confidence interval [CI], 2.13-4.71). A total of 8.3% of patients in the KHF cohort and 5.4% of patients in the non-KHF cohort underwent complex RD repair (CPT 67113) (P = 0.008; OR, 3.2; 95% CI, 1.13-2.25). When including all RD repair types (CPT 67108, 67110, 67107), the rate of PVR diagnosis was still significantly greater in the KHF cohort than in the non-KHF cohort (9.0% vs 4.2%, P < 0.01; OR, 2.28; 95% CI, 1.64-3.16). CONCLUSIONS: A dermatologic history of KHF may be a risk factor for PVR after RD repair. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

Factors Affecting Ophthalmology Trainees to Pursue Vitreoretinal Surgery Fellowship.

Objective The aim of this study was to understand the factors that ophthalmology trainees consider in pursuing vitreoretinal surgery (VRS) fellowship training. Methods This is a prospective observational survey study. Survey invitations were disseminated to postgraduate year 4 (PGY)-4 ophthalmology residents at Accreditation Council for Graduate Medical Education-accredited residency programs and surgical retina fellows at Association of University Professors of Ophthalmology Fellowship Compliance Committee-compliant fellowship programs in the United States. Survey questions on factors related to VRS were administered employing a 5-point Likert scale. Responses from ophthalmology residents pursuing surgical retina were combined with surgical retina fellows' responses and compared with responses from PGY-4 residents not pursuing vitreoretinal surgery. Results Eighty-one resident surveys were completed. Forty-three fellow surveys were completed. Fifty-seven out of eighty-one (70.4%) residents were not pursuing surgical retina, and a total of 67 trainees (24 residents, 43 fellows) were pursuing surgical retina. The following factors were associated with pursuing VRS training: male gender ( p = 0.031); having performed retina research during residency ( p ≤ 0.001); enjoying surgical retina procedures ( p ≤ 0.001), enjoying surgical retina patient outcomes ( p ≤ 0.001), and working with vitreoretinal surgeons ( p ≤ 0.001); finding surgical retina prestigious ( p ≤ 0.001); perceiving their residency having a strong record of matching surgical retina ( p = 0.039); liking the potential financial income from surgical retina ( p ≤ 0.001); and having vitreoretinal mentors during residency ( p = 0.014). A majority of trainees (31/57, 54.4%) not pursuing surgical retina disagreed or strongly disagreed with enjoying the patient outcomes in surgical retina. A third of female residents not pursuing surgical retina felt having a female surgical retina mentor would have made them more likely to pursue the field. Conclusion Longer retina rotations, encouraging resident participation in retina research, and increasing mentorship opportunities of female trainees from female retina specialists may increase resident interest in pursuing surgical retina fellowship.

Trends in Leadership and Award Recognition Among Women in the American Society of Retina Specialists.

Purpose: This work evaluates trends in achievement of women in the retina field, through an analysis of gender representation in the American Society of Retina Specialists (ASRS). Methods: This retrospective, longitudinal study spans 1983 to 2020. Historical data classified by male or female gender were collected from ASRS's overall membership, board of directors and officers, and recipients of the 4 society awards. The proportion of each benchmark held by women was compared with prior decades since the founding of ASRS using the Fisher's exact test. Results: Women's representation increased from 11% of ASRS members in 2007 to 19.7% in 2020. From 2010 to 2019, women received a higher proportion of society awards (21.1%) compared with membership prior to the start of that decade. In 2020, women were proportionally well represented in board of director positions (21.9%) and held a significantly higher proportion of board positions than in the period 1983 to 1989 (P = .02). From 1983 to 2020, women held 4.3% (1 of 23) of presidencies. Conclusions: Although the number of women in retina is increasing, women remain underrepresented in the leadership of ASRS. Interventions to increase exposure to female mentorship and improve childcare benefits are warranted to engage female ophthalmology trainees in retina and ultimately society leadership.

The Effect of Obstructive Sleep Apnea Treatment and Severity on Choroidal Thickness in Patients With Central Serous Chorioretinopathy.

Purpose: This work aimed to analyze the association of obstructive sleep apnea (OSA) with choroidal thickness (CT) in patients with central serous chorioretinopathy (CSC). Methods: We identified patients in the Stanford Research Repository with a diagnosis of CSC and OSA. Age- and sex-matched controls with either CSC or OSA only were also identified. CT was measured at 5 points (subfoveal, and 1500 and 3000 µm nasal and temporal) by 2 graders. In addition to OSA treatment and severity, we also investigated the association of Oxygen Desaturation Index and nocturnal oxygen saturation nadir with subfoveal CT (SFCT). Results: A total of 57 patients and 72 eyes met the study inclusion criteria. The mean SFCT was significantly different across the 3 groups: OSA-only was the thinnest, followed by CSC with OSA, and CSC-only was the thickest (194.2 µm, 295.1 µm, and 357.8 µm, respectively, P < .001). SFCT was thicker in CSC with OSA compared with those with only OSA (P < .05). OSA treatment status and OSA severity did not show a significant difference in SFCT in multivariable modeling. Nocturnal oxygen saturation nadir was positively associated with SFCT, but this did not reach significance.. Conclusions: SFCT is significantly different in patients with OSA alone, CSC with OSA, and CSC alone. While OSA treatment status did not demonstrate a significant difference in SFCT in this study, future studies should evaluate patients for OSA in patients known to have CSC and atypically thin CT to further investigate the novel metrics leveraged in this study.

Vitelliform Vitreoretinopathy: Clinical Implications of the Vitreomacular Interface.

Pathologies of the vitreomacular interface are implicated in a variety of sight-threatening clinical entities. The authors present a photo essay of a case of Terson syndrome with a striking premacular dehemoglobinized hemorrhage with ovoid morphology. This unique "vitelliform" finding highlights the distinct structure of the premacular vitreous space and its important implications in both health and disease.

The Effect of Obstructive Sleep Apnea on Absolute Risk of Central Serous Chorioretinopathy.

PURPOSE: To determine the incidence of central serous chorioretinopathy (CSC) stratified by age, sex, and diagnosis with obstructive sleep apnea (OSA), and to determine whether some patients with newly diagnosed CSC may be candidates for OSA evaluation. DESIGN: Retrospective cohort study. METHODS: We used the IBM MarketScan database to select 59,016,145 commercially insured patients in the United States between 2007 and 2016. We identified patients' first diagnosis with CSC, and defined patients as having OSA if they had a diagnosis following a sleep study. We specified Cox proportional hazard models with interactions between age, sex, and OSA status to determine patients' risk of developing CSC. We estimated the positive predictive value (PPV) that a new diagnosis of CSC would have in predicting a subsequent diagnosis of OSA. RESULTS: Risk of CSC increased with age in years (hazard ratio [HR] = 1.030, P < .001) and OSA diagnosis (HR = 1.081, P < .033), and was lower in women (HR = 0.284, P < .001). We estimated the annual incidence of CSC was 9.6 and 23.4 per 100,000 women and men, respectively. Incidence was higher in women and men with OSA (17.2 and 40.8 per 100,000). The PPV of CSC diagnosis as a predictor of OSA was highest in the fifth decade of life. CONCLUSION: The incidence of CSC in our patient sample is higher than previously reported. Risk of CSC is higher in men than in women, and OSA increases risk of CSC in both men and women. Some patients, particularly older male patients, may be good candidates for OSA evaluation following a CSC diagnosis.

Brolucizumab: Evolution through Preclinical and Clinical Studies and the Implications for the Management of Neovascular Age-Related Macular Degeneration.

Improving or maintaining visual acuity is the main goal for the treatment of neovascular age-related macular degeneration (nAMD). Current nAMD standard of care dictates frequent intravitreal (IVT) anti-vascular endothelial growth factor (VEGF) injections, which places a substantial burden on patients, caregivers, and physicians. Brolucizumab, a newly developed anti-VEGF molecule for nAMD treatment, has demonstrated longer durability and improvement in visual and anatomic outcomes in clinical studies in a q12-week regimen, indicating its potential to reduce treatment burden as an important therapeutic tool in nAMD management. This review focuses on the development of brolucizumab and the preclinical and clinical studies evaluating its efficacy, tolerability, and safety. Brolucizumab (also known as "RTH258" and "ESBA1008") is a humanized, single-chain variable fragment (scFv) antibody with a molecular mass of approximately 26 kDa that inhibits VEGF-A. Preclinical studies show that brolucizumab readily penetrates the retina to reach the retinal pigment epithelium (RPE)/choroid with minimal subsequent systemic exposure. The safety, tolerability, and efficacy of a single IVT brolucizumab administration in patients with treatment-naïve nAMD were first demonstrated in the SEE Phase 1/2 study. The OSPREY Phase 2 study showed brolucizumab to be as efficacious as aflibercept in a q8-week regimen with regard to best-corrected visual acuity (BCVA) and brolucizumab achieving greater fluid resolution. Brolucizumab-treated patients in the OSPREY study were subsequently challenged with a q12-week dosing interval, and the outcomes provided key information for the study design and end points of the Phase 3 studies. In the HAWK and HARRIER Phase 3 studies, after 3 monthly loading injections, brolucizumab treatment regimen (q12-week or q8-week) was guided by individual disease activity assessment using functional and anatomic parameters (central subfield thickness [CST], intraretinal fluid [IRF], or subretinal fluid [SRF]) versus aflibercept (q8-week). Fewer brolucizumab 6-mg treated eyes had disease activity versus aflibercept, and anatomic outcome results at weeks 16 and 48 demonstrate brolucizumab as a potent drying agent. Moreover, of patients treated with 6 mg brolucizumab, 55.6% and 51.0% maintained a q12-week dosing interval immediately after the loading phase until week 48 in HAWK and HARRIER, respectively. These Phase 3 studies demonstrated that the brolucizumab q12-week regimen maintains efficacy and safety while reducing treatment burden associated with regular IVT injections for patients with nAMD.

Nonmydriatic Photographic Screening for Diabetic Retinopathy in Pregnant Patients with Pre-Existing Diabetes in a Safety Net Population: 1 Year Results from the Diabetic Retinopathy in Pregnant Patients Study.

Background: Pregnant patients with pre-existing diabetes mellitus (DM) are at increased risk for development or progression of existing diabetic retinopathy (DR). A quality improvement project was initiated to improve DR screening during pregnancy at a safety net hospital. This article highlights the utility and generalizability of our telemedicine-based screening model. Materials and Methods: In April 2018, we implemented a photographic retinal screening system in the Maternal Fetal Medicine (MFM) clinic at Santa Clara Valley Medical Center in San Jose, CA. The system is intended to screen all pregnant patients with pre-existing diabetes (type 1 and 2). Retinal images are automatically uploaded to a secure server and interpreted by a retina specialist (C.K.P.). Results: A total of 71 pregnant patients with pre-existing DM were seen in the MFM clinic during the study period. Sixty-six of 71 patients (93.0%) were screened compared with 69.1% in the year prior. Of the 64 patients screened with readable images 11 (17.2%) had DR, whereas 53 did not. Forty-nine of the 64 (74.2%) patients screened underwent screening using the new nonmydriatic system in the MFM clinic. Only 7 out of 47 (14.9%) patients with readable images in the MFM clinic required referral to the ophthalmology clinic. Conclusion: Our model for DR screening in pregnant patients in safety net hospitals is effective in improving screening rates and expediting evaluation and treatment for those in need. This system can prevent irreversible vision loss in pregnant patients and provides an effective framework for ophthalmic care in a safety net hospital system.

ENDOGENOUS KLEBSIELLA PNEUMONIAE ENDOPHTHALMITIS IN NORTHERN CALIFORNIA.

PURPOSE: To report the clinical features, treatment modalities, and visual outcomes in 12 eyes with endogenous Klebsiella pneumoniae endophthalmitis (EKPE). METHODS: The medical records of all patients diagnosed with EKPE at Stanford Hospital (Palo Alto, CA) and Santa Clara Valley County Hospital (Santa Clara, CA) from January 2000 to March 2017 were retrospectively reviewed. RESULTS: A total of 10 patients (12 eyes) were diagnosed with EKPE. The median age at presentation was 56, 80% were male, and 30% were non-Asian. Presenting visual acuities ranged from 20/20 to no light perception. Of the 12 eyes 10 received a tap and injection (range, 1-33 injections per eye), 2 eyes underwent primary enucleation or evisceration, and 1 patient underwent pars plana vitrectomy after tap and injection. Final visual acuities ranged from no light perception (six eyes) to 20/300 or better (five eyes). Five patients eventually underwent evisceration or enucleation. All cases were associated with positive blood and/or vitreous cultures and had concurrent systemic infection. CONCLUSION: Endogenous Klebsiella pneumoniae endophthalmitis is a rare, but devastating, ocular infection. Most cases in this series resulted in light perception vision or worse, and almost half required enucleation or evisceration. In light of the virulence of EKPE, early diagnosis and treatment should be initiated in all suspected cases.

POLYPOIDAL CHOROIDAL VASCULOPATHY: A CLINICOPATHOLOGIC STUDY.

PURPOSE: To present a unique case of polypoidal choroidal vasculopathy presenting as a blind, painful eye with a suspected intraocular mass, and to correlate clinical findings with histopathologic studies. METHODS: Clinical case report and literature review. RESULTS: A 58-year-old Vietnamese man presented with a blind, painful eye with concern for an intraocular mass. B-scan ultrasonography showed massive intraocular hemorrhage and could not rule out a tumor. The patient underwent enucleation and the histopathologic findings were consistent with polypoidal choroidal vasculopathy. CONCLUSION: Polypoidal choroidal vasculopathy can present with dense vitreous hemorrhage and may masquerade as an intraocular mass. It can progress rapidly and lead to profound, irreversible vision loss. A diagnosis of polypoidal choroidal vasculopathy should be considered in patients of African or East Asian origin presenting with vitreous hemorrhage.

SMARTPHONE-BASED DILATED FUNDUS PHOTOGRAPHY AND NEAR VISUAL ACUITY TESTING AS INEXPENSIVE SCREENING TOOLS TO DETECT REFERRAL WARRANTED DIABETIC EYE DISEASE.

PURPOSE: To compare clinical assessment of diabetic eye disease by standard dilated examination with data gathered using a smartphone-based store-and-forward teleophthalmology platform. METHODS: 100 eyes of 50 adult patients with diabetes from a health care safety-net ophthalmology clinic. All patients underwent comprehensive ophthalmic examination. Concurrently, a smartphone was used to estimate near visual acuity and capture anterior and dilated posterior segment photographs, which underwent masked, standardized review. Quantitative comparison of clinic and smartphone-based data using descriptive, kappa, Bland-Altman, and receiver operating characteristic analyses was performed. RESULTS: Smartphone visual acuity was successfully measured in all eyes. Anterior and posterior segment photography was of sufficient quality to grade in 96 and 98 eyes, respectively. There was good correlation between clinical Snellen and smartphone visual acuity measurements (rho = 0.91). Smartphone-acquired fundus photographs demonstrated 91% sensitivity and 99% specificity to detect moderate nonproliferative and worse diabetic retinopathy, with good agreement between clinic and photograph grades (kappa = 0.91 ± 0.1, P < 0.001; AUROC = 0.97, 95% confidence interval, 0.93-1). CONCLUSION: The authors report a smartphone-based telemedicine system that demonstrated sensitivity and specificity to detect referral-warranted diabetic eye disease as a proof-of-concept. Additional studies are warranted to evaluate this approach to expanding screening for diabetic retinopathy.

Spontaneous resolution of clinically apparent submacular fluid after scleral buckling surgery.

A 37-year-old man presented with a chronic macula-involving rhegmatogenous retinal detachment. Despite scleral buckle surgery, the eye had clinically apparent submacular fluid for a prolonged period of time. By 1 year postoperatively, the patient had complete recovery of visual function, with residual ellipsoid layer changes on optical coherence tomography.

Morphologic features and evolution of inner retinal dimples on optical coherence tomography after internal limiting membrane peeling.

PURPOSE: To evaluate morphologic features and the evolution of inner retinal dimples using spectral domain optical coherence tomography after internal limiting membrane peeling. METHODS: A single-center retrospective study of spectral domain optical coherence tomography features in 43 eyes after full-thickness macular hole surgery with internal limiting membrane peeling without adjunctive internal limiting membrane staining. RESULTS: Postoperatively, a total of 210 dimples were noted in 37 eyes (86%), with a mean of 5.7 dimples per eye (median, 5; range, 1-20), most frequently located in the inferotemporal quadrant (n = 122, 58%, P < 0.0001). At initial detection, mean dimple dimensions were 199 µm wide (median, 183; range, 87-442 µm) and 19 µm deep (median, 17; range, 7-35 µm). During follow-up, mean maximum dimensions were 351 µm wide (median, 305; range, 219-494 µm) and 30 µm deep (median, 31; range, 15-55 µm). Dimple dimension reached a maximum at 12 months (median, 10; range, 2-22 months) followed by a modest decline. Mean preoperative and final postoperative visual acuity were 0.70 logMAR (median, 0.54; range, 0.09-1.4 logMAR) and 0.38 logMAR (median, 0.30; range, 0-1.4 logMAR), respectively. CONCLUSION: Inner retinal dimples are common after adjunct-free internal limiting membrane peeling and evolve in the postoperative period with enlargement over the first 12 months followed by reduction in size, and have no apparent impact on the visual acuity.

Embryonic stem cells as a treatment for macular degeneration.

INTRODUCTION: Retinal degenerations are typically characterized by loss of highly differentiated cell types within the neurosensory retina, such as photoreceptors, or retinal pigment epithelium (RPE). RPE loss is the final common pathway in a number of degenerations including the leading cause of new blindness in the developed world: age-related macular degeneration (AMD). AREAS COVERED: This paper presents the pathophysiologic case for RPE transplantation with stem cell (SC)-derived tissue, a review of the preclinical data substantiating the hypothesis and the initial clinical trials safety data from early human trials. EXPERT OPINION: Targeting the RPE for transplantation with SC-derived tissue presents a reasonable therapeutic opportunity in a variety of important, otherwise untreatable, blinding conditions. Success of cellular replacement strategies is contingent on finding a viable source of replacement cells, establishing a safe technique for delivery and survival of transplanted cells within the host, restoration of normal retinal architecture and stabilization or improvement of vision.

Peripheral fluorescein angiographic findings in fellow eyes of patients with branch retinal vein occlusion.

Introduction. Branch retinal vein occlusion (BRVO) is a common retinal vascular condition that results in intraocular inflammatory changes. Ultra wide field fluorescein angiography (UWFFA) is a retinal imaging device that can capture peripheral retinal findings. The purpose of this study was to look for peripheral findings in the fellow eye of patients with BRVO using UWFFA. Methods. Retrospective imaging review of patients diagnosed with BRVO that had both eyes imaged with UWFFA. Images were graded for peripheral findings in other quadrants of the same eye as well as in all quadrants of the fellow eye. Results. Of 81 patients, 14 (17%) patients had late vascular leakage in a quadrant other than the BRVO distribution. Five (6%) findings were in the same eye, 8 (10%) findings were in the fellow eye, and 1 (1%) finding was in both the same eye and the fellow eye. Of these 14 patients, 11 (80%) patients had hypertension. Conclusion. Late peripheral retinal leakage in the fellow eye of patients with BRVO was detected in this cohort of patients with UWFFA. This novel finding may represent underlying systemic inflammation, hypertension, or bilateral BRVOs.

Ocriplasmin for vitreoretinal diseases.

Fibronectin and laminin are clinically relevant plasmin receptors in the eye. Located at the vitreoretinal interface, they are cleaved by ocriplasmin (Microplasmin, ThromboGenics, Iselin, NJ), a novel ophthalmic medication. A series of clinical trials to study ocriplasmin for the treatment of vitreoretinal diseases such as vitreomacular traction, macular hole, and exudative age-related macular degeneration are underway. The results are promising and may impact patient care.

Embryonic stem cell trials for macular degeneration: a preliminary report.

BACKGROUND: It has been 13 years since the discovery of human embryonic stem cells (hESCs). Our report provides the first description of hESC-derived cells transplanted into human patients. METHODS: We started two prospective clinical studies to establish the safety and tolerability of subretinal transplantation of hESC-derived retinal pigment epithelium (RPE) in patients with Stargardt's macular dystrophy and dry age-related macular degeneration--the leading cause of blindness in the developed world. Preoperative and postoperative ophthalmic examinations included visual acuity, fluorescein angiography, optical coherence tomography, and visual field testing. These studies are registered with ClinicalTrials.gov, numbers NCT01345006 and NCT01344993. FINDINGS: Controlled hESC differentiation resulted in greater than 99% pure RPE. The cells displayed typical RPE behaviour and integrated into the host RPE layer forming mature quiescent monolayers after transplantation in animals. The stage of differentiation substantially affected attachment and survival of the cells in vitro after clinical formulation. Lightly pigmented cells attached and spread in a substantially greater proportion (>90%) than more darkly pigmented cells after culture. After surgery, structural evidence confirmed cells had attached and continued to persist during our study. We did not identify signs of hyperproliferation, abnormal growth, or immune mediated transplant rejection in either patient during the first 4 months. Although there is little agreement between investigators on visual endpoints in patients with low vision, it is encouraging that during the observation period neither patient lost vision. Best corrected visual acuity improved from hand motions to 20/800 (and improved from 0 to 5 letters on the Early Treatment Diabetic Retinopathy Study [ETDRS] visual acuity chart) in the study eye of the patient with Stargardt's macular dystrophy, and vision also seemed to improve in the patient with dry age-related macular degeneration (from 21 ETDRS letters to 28). INTERPRETATION: The hESC-derived RPE cells showed no signs of hyperproliferation, tumorigenicity, ectopic tissue formation, or apparent rejection after 4 months. The future therapeutic goal will be to treat patients earlier in the disease processes, potentially increasing the likelihood of photoreceptor and central visual rescue. FUNDING: Advanced Cell Technology.