Autosomal dominant neovascular inflammatory vitreoretinopathy with CAPN5 c.731T > C gene mutation; clinical management of a family cohort and review of the literature.

BACKGROUND: To report a cohort of patients with clinically and genetically diagnosed autosomal dominant neovascular inflammatory vitreoretinopathy (ADNIV) and showcase the spectrum of the disease utilizing multimodal imaging and genetic testing. Additionally, the utility of multimodal imaging in guiding treatment will also be illustrated. MATERIALS/METHODS: Five patients from a single-family pedigree in Ohio with clinical signs of ADNIV were evaluated. Medical history, family history, and complete ocular examinations were obtained during regular clinic visits. Multimodal imaging including ocular coherence tomography, fluorescein angiography, wide-field fundus photographs, and Humphrey visual field testing was obtained for all five patients. Additionally, genetic testing for the Calpain-5 (CAPN5) gene was conducted on all patients. RESULTS: All five patients were noted to have a CAPN5 c.731T > C (p.L244P) mutation on genetic testing. Using multimodal imaging to supplement the clinical examination, pathologic changes such as retinal vascular inflammation, macular edema, and tractional retinal membranes were well illustrated and monitored over time. This allowed for earlier intervention when appropriate such as with intraocular steroid or systemic anti-inflammatory treatments. CONCLUSION: Phenotypic presentation varied among patients in this series, but is consistent with the spectrum of pathologic changes previously described in patients with other CAPN5 gene mutations. Monitoring of patients with ADNIV utilizing multimodal imaging can help better assess progression of this disease and guide treatment decisions. Additionally, increased genetic testing in patients with inherited retinal diseases may reveal novel gene mutations that could serve as potential targets for future genetic treatment regimens.

DIRECT MACULAR HOLE MANIPULATION RESULTS IN HIGH SUCCESS RATE IN SECONDARY MACULAR HOLE REPAIR.

PURPOSE: To investigate closure rates and functional outcomes of surgery for refractory and recurrent macular holes (MHs) in a real-world setting. METHODS: Retrospective review of secondary MH surgeries. RESULTS: A total of 72 eyes from 72 patients were included. Eyes had a mean of 1.51 surgeries before inclusion into this study with a mean MH size of 762 µ m and a mean baseline logarithm of the minimum angle of resolution best-corrected visual acuity of 1.11 (∼20/260 Snellen). Closure rates were 89.3% for tissue transplantation, 77.3% for internal limiting membrane (ILM) flaps, 92.9% for MH manipulation, and 12.5% for repeat ILM peeling ( P < 0.05). Best-corrected visual acuity changes in logarithm of the minimum angle of resolution from baseline to postoperative month six were +0.29 for ILM peeling alone (15 Early Treatment Diabetic Retinopathy Study letters worse), -0.39 for MH manipulation (20 Early Treatment Diabetic Retinopathy Study letters improved), -0.23 for tissue transplantation (13 Early Treatment Diabetic Retinopathy Study letters improved), and -0.2 for ILM flaps (10 Early Treatment Diabetic Retinopathy Study letters improved; P < 0.05). CONCLUSION: Secondary MH closure is possible using various surgical techniques with acceptable anatomical closure rates. Repeat ILM peeling is associated with the lowest closure rates and poorest functional results. To distinguish between techniques would require a large sample size of approximately 750 eyes.

Bilateral papillitis as the initial presentation of neurosyphilis in a patient previously treated for primary and secondary syphilis.

Purpose: To report a patient previously treated for primary and secondary syphilis who presented with papillitis. The patient was found to have neurosyphilis likely due to inadequate treatment of primary and secondary syphilis. Observations: A 60-year-old male with human immunodeficiency virus (HIV) and hepatitis C was referred for evaluation of blurry vision for the past several months. Anterior segment examination was notable for 1+ diffuse non-granulomatous keratic precipitates and 2+ flare with trace cell in both eyes. Dilated fundus exam revealed grade 2 optic disc edema in both eyes with no evidence of infectious retinitis. He was recently treated for syphilis with a single dose of intramuscular (IM) penicillin. These findings were consistent with syphilitic papillitis likely secondary to neurosyphilis. The patient underwent a lumbar puncture which confirmed the diagnosis of neurosyphilis. He was admitted to the hospital for intravenous (IV) penicillin. He later revealed a prior history of syphilis that was treated 3 years ago and 1 year ago. Conclusions and importance: Ocular syphilis can have a wide variety of presentations. Any patient with syphilis and uveitis should have prompt work up for neurosyphilis. Patients with any stage of syphilis need close follow up with repeat titers after treatment to ensure adequate treatment and prevent progression and permanent ocular or neurologic sequelae.

Efficient labeling of retinal fundus photographs using deep active learning.

Purpose: To compare the performance of four deep active learning (DAL) approaches to optimize label efficiency for training diabetic retinopathy (DR) classification deep learning models. Approach: 88,702 color retinal fundus photographs from 44,351 patients with DR grades from the publicly available EyePACS dataset were used. Four DAL approaches [entropy sampling (ES), Bayesian active learning by disagreement (BALD), core set, and adversarial active learning (ADV)] were compared to conventional naive random sampling. Models were compared at various dataset sizes using Cohen's kappa (CK) and area under the receiver operating characteristic curve on an internal test set of 10,000 images. An independent test set of 3662 fundus photographs was used to assess generalizability. Results: On the internal test set, 3 out of 4 DAL methods resulted in statistically significant performance improvements ( p < 1 × 10 - 4 ) compared to random sampling for multiclass classification, with the largest observed differences in CK ranging from 0.051 for BALD to 0.053 for ES. Improvements in multiclass classification generalized to the independent test set, with the largest differences in CK ranging from 0.126 to 0.135. However, no statistically significant improvements were seen for binary classification. Similar performance was seen across DAL methods, except ADV, which performed similarly to random sampling. Conclusions: Uncertainty-based and feature descriptor-based deep active learning methods outperformed random sampling on both the internal and independent test sets at multiclass classification. However, binary classification performance remained similar across random sampling and active learning methods.

A SYSTEMATIC REVIEW OF DEEP LEARNING APPLICATIONS FOR OPTICAL COHERENCE TOMOGRAPHY IN AGE-RELATED MACULAR DEGENERATION.

PURPOSE: To survey the current literature regarding applications of deep learning to optical coherence tomography in age-related macular degeneration (AMD). METHODS: A Preferred Reporting Items for Systematic Reviews and Meta-Analyses systematic review was conducted from January 1, 2000, to May 9, 2021, using PubMed and EMBASE databases. Original research investigations that applied deep learning to optical coherence tomography in patients with AMD or features of AMD (choroidal neovascularization, geographic atrophy, and drusen) were included. Summary statements, data set characteristics, and performance metrics were extracted from included articles for analysis. RESULTS: We identified 95 articles for this review. The majority of articles fell into one of six categories: 1) classification of AMD or AMD biomarkers (n = 40); 2) segmentation of AMD biomarkers (n = 20); 3) segmentation of retinal layers or the choroid in patients with AMD (n = 7); 4) assessing treatment response and disease progression (n = 13); 5) predicting visual function (n = 6); and 6) determining the need for referral to a retina specialist (n = 3). CONCLUSION: Deep learning models generally achieved high performance, at times comparable with that of specialists. However, external validation and experimental parameters enabling reproducibility were often limited. Prospective studies that demonstrate generalizability and clinical utility of these models are needed.

Secondary glaucoma in CAPN5-associated neovascular inflammatory vitreoretinopathy.

OBJECTIVE: The objective of this study was to review the treatment outcomes of patients with secondary glaucoma in cases of autosomal dominant neovascular inflammatory vitreoretinopathy (ADNIV), a hereditary autoimmune uveitis due to mutations in CAPN5. PATIENTS AND METHODS: A retrospective, observational case series was assembled from ADNIV patients with secondary glaucoma. The main outcome measures were intraocular pressure (IOP), visual acuity, use of antiglaucoma medications, ocular surgeries, and adverse outcomes. Perimetry and optic disk optical coherence tomography (OCT) were also analyzed. RESULTS: Nine eyes of five ADNIV patients with secondary glaucoma were reviewed. Each received a fluocinolone acetonide (FA) implant for the management of posterior uveitis. Following implantation, no eyes developed neovascular glaucoma. Five eyes (in patients 1, 2, and 5) required Ahmed glaucoma valve surgery for the management of steroid-responsive glaucoma. Patient 2 also developed angle closure with iris bombe and underwent laser peripheral iridotomy. Patient 4 had both hypotony and elevated IOP that required periodic antiglaucoma medication in the FA-implanted eye. Patient 3 did not develop steroid-response glaucoma in either eye. Optic disk examinations were obscured by fibrosis and better assessed with OCT. CONCLUSION: ADNIV patients show combined mechanism secondary glaucoma best assessed by OCT of the optic disk. The FA implants have reduced uveitic and neovascular glaucoma. Nevertheless, IOP management remains complex due to steroid-response glaucoma, angle closure glaucoma, and hypotony.

Surgical management of fibrotic encapsulation of the fluocinolone acetonide implant in CAPN5-associated proliferative vitreoretinopathy.

OBJECTIVE: To review fibrosis of fluocinolone acetonide (FA) implants in subjects with CAPN5 autosomal dominant neovascular inflammatory vitreoretinopathy (ADNIV). METHODS: A retrospective case series was assembled from ADNIV patients in which there was fibrotic encapsulation of a fluocinolone acetonide implant. CAPN5 genotypes and surgical repair techniques were reviewed. RESULTS: Two eyes of two ADNIV patients developed a fibrotic capsule over the fluocinolone acetonide implant. Both patients had Stage IV disease. Patient A had a c.731T > C mutation in the CAPN5 gene and patient B had a c.728G > T mutation. The fibrotic membrane was surgically excised and the implant function was restored. CONCLUSION: The exuberant fibrotic response in later stages of ADNIV may be resistant to local immunosuppression with steroids. Surgical excision of fibrotic membranes over FA implants can reestablish local steroid delivery in cases of severe proliferative vitreoretinopathy.