Sex Distributions in Non-ABCA4 Autosomal Macular Dystrophies.

Purpose: We sought to explore whether sex imbalances are discernible in several autosomally inherited macular dystrophies. Methods: We searched the electronic patient records of our large inherited retinal disease cohort, quantifying numbers of males and females with the more common (non-ABCA4) inherited macular dystrophies (associated with BEST1, EFEMP1, PROM1, PRPH2, RP1L1, and TIMP3). BEST1 cases were subdivided into typical autosomal dominant and recessive disease. For PRPH2, only patients with variants at codons 172 or 142 were included. Recessive PROM1 and recessive RP1L1 cases were excluded because these variants give a more widespread or peripheral degeneration. The proportion of females was calculated for each condition; two-tailed binomial testing was performed. Where a significant imbalance was found, previously published cohorts were also explored. Results: Of 325 patients included, numbers for BEST1, EFEMP1, PROM1, PRPH2, RP1L1, and TIMP3 were 152, 35, 30, 50, 14, and 44, respectively. For autosomal dominant Best disease (n = 115), there were fewer females (38%; 95% confidence interval [CI], 29-48%; P = 0.015). For EFEMP1-associated disease (n = 35), there were significantly more females (77%; 95% CI, 60%-90%; P = 0.0019). No significant imbalances were seen for the other genes. When pooling our cohort with previous large dominant Best disease cohorts, the proportion of females was 37% (95% CI, 31%-43%; P = 1.2 × 10-5). Pooling previously published EFEMP1-cases with ours yielded an overall female proportion of 62% (95% CI, 54%-69%; P = 0.0023). Conclusions: This exploratory study found significant sex imbalances in two autosomal macular dystrophies, suggesting that sex could be a modifier. Our findings invite replication in further cohorts and the investigation of potential mechanisms.

Pseudoxanthoma elasticum and retinitis pigmentosa in a patient with a novel mutation in the ABCC6 gene.

BACKGROUND: Pseudoxanthoma elasticum (PXE) is an autosomal recessive condition caused by mutations in the ABCC6 gene. Ocular features include angioid streaks, peau d'orange fundus, and drusen. We report a novel ABCC6 mutation causing PXE in a patient with a mixed phenotype of PXE and retinitis pigmentosa (RP). CASE: A 37-year-old female presented with decreased peripheral vision and nyctalopia. Ocular imaging revealed angioid streaks emanating from the optic nerve as well as peripheral pigmentary changes and bone spicules. Genetic testing revealed two mutations in ABCC6 in trans. No other mutation was identified. CONCLUSION: We present a rare case with ocular findings of PXE and RP in a patient with a novel ABCC6 mutation. The patient presented both with peripheral pigmentary changes and angioid streaks. Further investigation into this novel mutation would be beneficial to determine if the mutation is involved in the RP phenotype.

Comparison of Endophthalmitis Rates after Alcohol-Based Chlorhexidine and Povidone-Iodine Antisepsis for Intravitreal Injections.

OBJECTIVE: Intravitreal injections (IVIs) are the most frequently performed intraocular procedure in Canada. Povidone-iodine (PI) is the current gold standard for antisepsis for IVI and is widely used; chlorhexidine (CH) is a possible alternative antiseptic agent. This study aims to compare rates of endophthalmitis after IVI with 0.05% chlorhexidine with a 4% alcohol base antisepsis to rates of endophthalmitis after IVI with 10% PI antisepsis. DESIGN: Retrospective cohort study. SUBJECTS: Eyes that received IVI between May 2019 and October 2022 at a group retina practice in Edmonton, Canada. METHODS: Eyes at a single center received focal conjunctival application of either 10% PI antisepsis or 0.05% CH in 4% alcohol antisepsis for 30 seconds before each IVI. MAIN OUTCOME MEASURE: Rates of endophthalmitis between the PI and CH groups. RESULTS: A total of 170 952 IVIs were performed during the study period. A total of 31 135 were performed using CH prophylaxis compared with 139 817 with PI prophylaxis. Among all IVIs there were 49 total cases of endophthalmitis, 29 in the PI group (0.021%) and 20 in the CH group (0.064%). There was a statistically significant difference in the rates of endophthalmitis between the 2 groups (P < 0.001). The odds ratio for developing endophthalmitis with CH antisepsis was 3.1 (95% confidence interval, 1.9-5.2) compared with PI antisepsis. There were increased odds of developing endophthalmitis with aflibercept injection compared with bevacizumab (odds ratio, 3.48; 95% confidence interval, 2.09-7.24). CONCLUSIONS: There is a statistically significant difference in rates of endophthalmitis between alcohol-based CH and PI antisepsis for IVI in our patient population utilizing the methods discussed. In our center, alcohol-based CH is now considered a second-line antiseptic agent. Further studies are warranted to further assess the endophthalmitis rate utilizing these 2 antiseptic agents. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

UTILIZATION OF PREOPERATIVE MIDPERIPHERAL OPTICAL COHERENCE TOMOGRAPHY FOR TAILORED SURGICAL MANAGEMENT OF PROLIFERATIVE VITREORETINOPATHY.

PURPOSE: The purpose of this study was to report on the use of preoperative spectral domain optical coherence tomography to assess retinal pathology and guide the surgical approach to proliferative vitreoretinopathy. METHODS: A case report was discussed. RESULTS: A 70-year-old man developed proliferative vitreoretinopathy after surgical repair of a macula-off rhegmatogenous retinal detachment. In preparation for further surgery, inferior preretinal fibrosis and membranes were identified on preoperative optical coherence tomography. The patient underwent successful vitrectomy with peeling of the membranes resulting in markedly improved visual acuity. CONCLUSION: Widely available spectral domain optical coherence tomography can be used preoperatively to image the midperipheral retina and guide surgical decision-making in the management of proliferative vitreoretinopathy.

Visual and Anatomical Outcomes of a Single Intravitreal Dexamethasone in Diabetic Macular Edema: An 8 Year Real-World Study.

IMPORTANCE: Diabetic macular edema (DME) is a major cause of vision loss in patients with diabetes mellitus. Intravitreal dexamethasone is a treatment option for patients unsuitable for or non-responsive to anti-angiogenic agents. OBJECTIVE: To quantify visual and anatomical outcomes from an initial intravitreal dexamethasone injection over the expected 6-month period of dexamethasone release by the implant. Design and enrolment: This is a retrospective cohort study using electronic medical records of patients reviewed between 1 January 2012 and 1 April 2022. SETTING: A tertiary eye-care center in London, United Kingdom; Moorfields Eye Hospital National Healthcare System Foundation Trust. PARTICIPANTS: The cohort comprised 418 adult patients with DME who received an initial treatment of 700 µg intravitreal dexamethasone in the study period. Of these, 240 patients met the inclusion criteria of ≥2 hospital visits following initial injection (≥1 beyond 6 months) and no previous ocular corticosteroid treatment or missing assessment at baseline. EXPOSURE(S): Intravitreal dexamethasone implant (700 µg). MAIN OUTCOME(S) AND MEASURE(S): Probability of a positive visual outcome, defined as ≥5 or ≥10 Early Treatment Diabetic Retinopathy Study (ETDRS)-letter gain after treatment when compared to baseline (Kaplan-Meier models). RESULTS: From the initial intravitreal dexamethasone injection alone, we observed a >75% chance of gaining ≥5 ETDRS letters and >50% chance of gaining ≥10 ETDRS letters within 6 months. There was less than a 50% chance of sustaining either positive visual outcome beyond 4 months. CONCLUSIONS AND RELEVANCE: Most patients can be expected to have a positive visual outcome following an initial injection of dexamethasone implants that subsides within 4 months. Real-world re-treatment was observed to be delayed until after visual benefits were lost in half of the cohort. Further research will be needed to study the effects of delays in re-treatment.

Formal registration of visual impairment in people with diabetic retinopathy significantly underestimates the scale of the problem: a retrospective cohort study at a tertiary care eye hospital service in the UK.

AIMS: To analyse the prevalence of visual impairment (VI), compare it to certification of visual impairment (CVI) and analyse VI associations in patients with diabetic retinopathy (DR). METHODS: Retrospective cohort study, which included 8007 patients with DR referred from the English diabetic eye screening programme to a tertiary referral eye hospital. Main outcome measure was VI, defined as vision in the best eye of <6/24. We conducted a multivariable logistic regression for VI as primary outcome of interest, controlling for age, sex, type of diabetes, baseline DR grade, ethnicity and index of multiple deprivation (IMD). RESULTS: Mean age was 64.5 (SD 13.6) years; 61% of patients were men; and 31% of South Asian ethnicity. There were 68 patients with CVI during the study period, and 84% (272/325) of patients with VI did not have CVI after a mean follow-up of 1.87 (SD ±0.86) years. Older age showed a positive association with VI (OR per decade rise 1.88, 95% CI 1.70 to 2.08; p=1.8×10-34). Men had a lower risk of VI (OR 0.62, 95% CI 0.50 to 0.79, p=6.0×10-5), and less deprivation had a graded inverse association with VI (OR per IMD category increase 0.83, 95% CI 0.74 to 0.93, p value for linear trend 0.002). CONCLUSION: The majority of people with vision impairment are not registered at the point of care, which could translate to underestimation of diabetes-related VI and all-cause VI at a national level if replicated at other centres. Further work is needed to explore rates of VI and uptake of registration.

Training Deep Learning Models to Work on Multiple Devices by Cross-Domain Learning with No Additional Annotations.

PURPOSE: To create an unsupervised cross-domain segmentation algorithm for segmenting intraretinal fluid and retinal layers on normal and pathologic macular OCT images from different manufacturers and camera devices. DESIGN: We sought to use generative adversarial networks (GANs) to generalize a segmentation model trained on one OCT device to segment B-scans obtained from a different OCT device manufacturer in a fully unsupervised approach without labeled data from the latter manufacturer. PARTICIPANTS: A total of 732 OCT B-scans from 4 different OCT devices (Heidelberg Spectralis, Topcon 1000, Maestro2, and Zeiss Plex Elite 9000). METHODS: We developed an unsupervised GAN model, GANSeg, to segment 7 retinal layers and intraretinal fluid in Topcon 1000 OCT images (domain B) that had access only to labeled data on Heidelberg Spectralis images (domain A). GANSeg was unsupervised because it had access only to 110 Heidelberg labeled OCTs and 556 raw and unlabeled Topcon 1000 OCTs. To validate GANSeg segmentations, 3 masked graders manually segmented 60 OCTs from an external Topcon 1000 test dataset independently. To test the limits of GANSeg, graders also manually segmented 3 OCTs from Zeiss Plex Elite 9000 and Topcon Maestro2. A U-Net was trained on the same labeled Heidelberg images as baseline. The GANSeg repository with labeled annotations is at https://github.com/uw-biomedical-ml/ganseg. MAIN OUTCOME MEASURES: Dice scores comparing segmentation results from GANSeg and the U-Net model with the manual segmented images. RESULTS: Although GANSeg and U-Net achieved comparable Dice scores performance as human experts on the labeled Heidelberg test dataset, only GANSeg achieved comparable Dice scores with the best performance for the ganglion cell layer plus inner plexiform layer (90%; 95% confidence interval [CI], 68%-96%) and the worst performance for intraretinal fluid (58%; 95% CI, 18%-89%), which was statistically similar to human graders (79%; 95% CI, 43%-94%). GANSeg significantly outperformed the U-Net model. Moreover, GANSeg generalized to both Zeiss and Topcon Maestro2 swept-source OCT domains, which it had never encountered before. CONCLUSIONS: GANSeg enables the transfer of supervised deep learning algorithms across OCT devices without labeled data, thereby greatly expanding the applicability of deep learning algorithms.

Relentlessly Progressive Sweet Syndrome of the Eye with Scleritis and Choroidal Infiltration.

PURPOSE: To describe a case of Sweet syndrome, a dermatologic inflammatory disease, with progressive, unrelenting ocular findings. METHODS: Case report. RESULTS: A 73-year-old male was evaluated with a six-month history of Sweet syndrome, manifesting as cutaneous erythematous edematous papules on the dorsal arms and shins and confirmed with biopsy demonstrating neutrophil infiltration with nuclei fragmentation and lack of vasculitis. He initially noted a unilateral red eye with ocular pain and was found to have scleritis and choroidal infiltration. The patient's ocular disease progressed despite treatment with systemic corticosteroids, intraocular Ozurdex ®, systemic dapsone, and subtenons triamcinolone. Systemic evaluation was negative for malignancy or other inflammatory syndromes. Following 7 months of non-manageable ocular pain enucleation was offered to the patient, but he declined. CONCLUSION: Sweet syndrome, a dermatologic condition, can be associated with unilateral scleritis and choroidal infiltration that are relentlessly progressive despite maximal systemic and ocular corticosteroid therapy.

Unilateral benign yellow dot maculopathy.

PURPOSE: To describe a unique case of unilateral benign yellow dot maculopathy. OBSERVATIONS: A 25-year-man was evaluated after incidental finding of yellow dots in the right macula. The findings of examination and multimodal imaging were in keeping with a diagnosis of benign yellow dot maculopathy. CONCLUSIONS AND IMPORTANCE: Benign yellow dot maculopathy is a recently described entity with either a sporadic or dominant inheritance pattern. This is the first known report of the characteristic findings of this phenotype presenting unilaterally.

A Case of Transient Monocular Vision Loss and Paracentral Acute Middle Maculopathy.

ABSTRACT: A 77-year-old man with multiple cerebrovascular risk factors presented with a history of transient monocular vision loss and residual paracentral visual disturbance in the right eye. Carotid ultrasounds, erythrocyte sedimentation rate, and C-reactive protein were all within normal limits. He was found to have retinal whitening within the macula in the right eye, corresponding to an area of decreased retinal perfusion on optical coherence topography (OCT)-angiography and a hyperreflective middle retina band on spectral domain-OCT. This was consistent with a diagnosis of paracentral acute middle maculopathy (PAMM). PAMM should be considered a part of the differential diagnosis in patients with focal visual disturbances, and OCT studies are recommended as part of the work up as subtle fundus findings may be missed.

Ultra-Widefield Imaging of Peripheral Vascular Abnormalities in Idiopathic Macular Telangiectasia Type 1.

Purpose: This work reports unusual peripheral vascular anomalies on ultra-widefield angiography in a case of idiopathic macular telangiectasia (IMT) type 1. Methods: A case report is discussed. Results: A 51-year-old woman with a 6-year history of IMT type 1 presented with ongoing vision symptoms from persistent macular edema despite extended antivascular endothelial growth factor therapy. Examination and macular imaging findings were consistent with a diagnosis of IMT type 1, and ultra-widefield angiography additionally demonstrated nonperfusion, terminal vascular loops, and arteriovenous anastomosis without exudation or telangiectasis. The patient's condition remained stable after she elected observation. Conclusion: While extrafoveal vascular anomalies are a known feature of IMT type 1, they commonly consist of peripheral telangiectasias and exudation. Describing new peripheral vascular abnormalities in IMT adds to our knowledge of this condition and could be of value for diagnosis, management, and further study.

Serpiginous Choroiditis Presenting in Association With Clostridium difficile Infection and Ulcerative Colitis.

Purpose: This work reports a case of serpiginous choroiditis (SC) in association with ulcerative colitis and Clostridium difficile infection. Methods: A case report is discussed. Results: A 35-year-old man with a history of ulcerative colitis and recently treated C difficile infection presented with a rapid decline in central visual acuity in both eyes. Examination findings included geographic creamy-white lesions extending from the peripapillary region in both eyes. Multimodal imaging and negative infectious workup results supported the diagnosis of SC. Visual acuity and examination findings improved after initiation of systemic prednisone therapy. Adalimumab was initiated as a steroid-sparing treatment. At the last follow-up, 5 months after the initial presentation, SC and ulcerative colitis both remain in remission. Conclusions: SC has been previously described in patients with systemic disorders, including autoimmune conditions. This patient developed SC following C difficile infection and in the context of active ulcerative colitis. To our knowledge, this is the first report of SC in association with these entities.