Prevalence of Age-Related Macular Degeneration in Patients with Chronic Exposure to P2X7R Inhibitors.

PURPOSE: P2X7 receptor (P2X7R) is a purinergic cation channel whose activation has been linked with age-related macular degeneration (ARMD). Several nucleoside reverse transcriptase inhibitors, zidovudine (AZT), lamivudine (3TC) and abacavir (ABC), have been shown to inhibit P2X7R and improve outcomes in animal models of ARMD. Our aim is to investigate the association between chronic AZT, 3TC, and ABC therapy and ARMD in a clinical setting. METHODS: This is a retrospective cohort study comparing 445 patients with HIV and confirmed usage of AZT, 3TC, and ABC against 200 patients with HIV without usage of AZT, 3TC, and ABC and 445 non-HIV infected patients. Fundus examination and spectral domain optical coherence tomography (SD-ODT) were used to measure prevalence of early-intermediate stage ARMD, geographic atrophy, and exudative ARMD. RESULTS: There was no statistically significant difference in the prevalence of early-intermediate stage ARMD between the HIV infected patients with a history of AZT, 3TC, and ABC use and the HIV infected patients without AZT, 3TC, and ABC use (p = 0.887). There was also no statistically significant difference in the prevalence of geographical atrophy (p = 0.062) and exudative AMD (p > 0.999) between the HIV infected patients with a history of AZT, 3TC, and ABC use and non-HIV infected patients. CONCLUSION: We did not find an effect of P2X7R inhibiting antiretrovirals usage on early-intermediate stage ARMD, geographical atrophy, or exudative ARMD. Studies with larger cohort and more rigorous medication history are needed to assess the effects on geographical atrophy or exudative ARMD.

TECHNIQUE FOR REMOVAL OF A GANCICLOVIR IMPLANT DISLOCATED IN THE VITREOUS CAVITY.

PURPOSE: To report a technique to remove a dislocated ganciclovir implant in the vitreous cavity. METHODS: Retrospective case series. Two patients with dislocated ganciclovir implants in the vitreous cavity. RESULTS: A 6-mm pars plana incision was made; the soft tip was used to elevate the implant behind the intraocular lens and then 0.12-mm forceps were used to externalize the implant. The implant was successfully removed in both patients. CONCLUSION: Removal of a dislocated ganciclovir implant with its encasing strut can be effectively retrieved using a bimanual approach.

NOVEL MFRP MUTATION WITH NANOPHTHALMOS, OPTIC DISK DRUSEN, AND PERIPHERAL RETINOSCHISIS IMAGED WITH ULTRA-WIDEFIELD OPTICAL COHERENCE TOMOGRAPHY.

PURPOSE: To describe with multimodal imaging including the use of ultra-widefield optical coherence tomography imaging a distinct phenotype of autosomal recessive nanophthalmos associated with a novel mutation of the MFRP gene (membrane-type frizzled-related protein). METHODS: Case report of a single patient followed by the Weill Cornell Medicine Department of Ophthalmology Retina and Glaucoma Services, and review of the relevant literature. RESULTS: A patient with a novel homozygous mutation in the MFRP gene (c.472C>T) presented with nanophthalmos, optic disk drusen, foveal hypoplasia, and extensive peripheral retinoschisis, which was revealed to be multilevel retinoschisis on ultra-widefield optical coherence tomography. Unlike other reported cases, the findings associated with this novel mutation did not include foveoschisis or clinically obvious retinitis pigmentosa. The patient underwent prophylactic peripheral laser iridotomy in both eyes. CONCLUSION: Here, we present a patient with nanophthalmos, optic disk drusen, and foveal hypoplasia associated with extensive peripheral retinoschisis imaged by ultra-widefield optical coherence tomography, but not foveal retinoschisis or prominent retinitis pigmentosa. The findings may expand the clinical spectrum of MFRP -associated nanophthalmos.

Advancements in ocular gene therapy delivery: vectors and subretinal, intravitreal, and suprachoroidal techniques.

INTRODUCTION: Ocular gene therapy represents fertile ground for rapid innovation, with ever-expanding therapeutic strategies, molecular targets, and indications. AREAS COVERED: Potential indications for ocular gene therapy have classically focused on inherited retinal disease (IRD) but more recently include acquired retinal diseases, such as neovascular age-related macular degeneration, geographic atrophy, and diabetic retinopathy. Ocular gene therapy strategies have proliferated recently, and include gene augmentation, gene inactivation, gene editing, RNA modulation, and gene-independent gene augmentation. Viral vector therapeutic constructs include adeno-associated virus and lentivirus and continue to evolve through directed evolution and rationale design. Ocular gene therapy administration techniques have expanded beyond pars plana vitrectomy with subretinal injection to intravitreal injection and suprachoroidal injection. EXPERT OPINION: The success of treatment for IRD, paired with the promise of clinical research in acquired retinal diseases and in administration techniques, has raised the possibility of in-office gene therapy for common retinal disorders within the next 5 to 10 years.

Automated Retinal Layer Segmentation in CLN2-Associated Disease: Commercially Available Software Characterizing a Progressive Maculopathy.

Purpose: CLN2-associated disease is a hereditary, fatal lysosomal storage disorder characterized by progressive brain and retinal deterioration. Here, we characterize the inner and outer retinal degeneration using automated segmentation software in optical coherence tomography scans, providing an objective, quantifiable metric for monitoring subtle changes previously identified with a validated disease classification scale (the Weill Cornell Batten Scale). Methods: This study is a retrospective, single-center cohort review of images from examinations under anesthesia in treatment-naïve patients with CLN2-associated disease. Automated segmentation software was used to delineate retinal nerve fiber, ganglion cell layer (GCL), and outer nuclear layer (ONL) thickness measurements in the fovea, parafovea, and perifovea based on age groups (months): 30 to 38, 39 to 45, 46 to 52, 53 to 59, 60 to 66, and 67 or older. Results: Twenty-seven eyes from 14 patients were included, with 8 serial images yielding 36 interpretable optical coherence tomography scans. There was a significant difference in parafoveal ONL thickness between 39 to 45 and 46 to 52 months of age (P = 0.032) not seen in other regions or retinal layers. Perifoveal ONL demonstrated a difference in thickness between the 60 to 66 and greater than 67 months age cohorts (P = 0.047). There was strong symmetry between eyes, and high segmentation repeatability. Conclusions: Parafoveal ONL thickness represents a sensitive, early age indicator of CLN2-associated degeneration. Outer retinal degeneration is apparent at younger ages than inner retinal changes though in treatment-naïve patients all retinal layers showed significant differences between 60 to 66 and more than 67 months of age. Translational Relevance: This study establishes sensitive, quantitative biomarkers for assessing retinal degeneration in a large cohort natural history study in anticipation of future clinical trials.

Quantitative Modeling of Ultra-Widefield Choroidal Indocyanine Green Angiography in Systemic Vascular Diseases.

BACKGROUND AND OBJECTIVE: To evaluate quantitative measurements of choroidal vasculature as obtained via ultra-widefield indocyanine green angiography (ICGA) in patients with systemic vascular diseases. PATIENTS AND METHODS: Retrospective chart review and image analysis of 38 eyes from 21 patients with ICGA as part of routine retinal care. Images were binarized with lines drawn at specific antero-posterior landmarks. The vessel density and mean vessel caliber were measured along these lines and correlated with systemic vascular disease status. RESULTS: Unlike those with other systemic vascular diseases, patients with obstructive sleep apnea (OSA) were found to have increased choroidal vascular density and vessel caliber in all measurements of the peripheral choroid compared with those patients without (P < .05 for all measurements). CONCLUSIONS: Patients with OSA may have increased vascular density secondary to increased choroidal vessel caliber. Further work is needed to validate the modeling and confirm the association. [Ophthalmic Surg Lasers Imaging Retina. 2021;52:281-287.].

Case Report: Glaucoma in an Infant With Retinopathy of Prematurity.

Retinopathy of prematurity (ROP) is a leading cause of childhood blindness that occurs due to incomplete development of retinal blood vessels in preterm infants. Glaucoma is an ocular comorbidity in some patients with ROP, and it may be associated with immature anterior chamber development, ROP itself, or the treatment for ROP. There have been a few reports of narrow-angle glaucoma after laser treatment for ROP. In this case report, we describe the course of a female infant born at 24 weeks and 5 days of gestational age with treatment-requiring ROP treated with laser photocoagulation who subsequently developed very elevated intraocular pressure and shallow anterior chambers without pupillary block. The patient required bilateral ab externo trabeculotomy for elevated intraocular pressure, which normalized after the procedure. The patient has remained stable at the last follow-up at 51 weeks postmenstrual age. Differing from previous glaucoma presentations in this setting, we illustrate a case of elevated intraocular pressure and anterior chamber narrowing after laser therapy without pupillary block or synechiae. The possible multifactorial etiology of glaucoma in this patient, including incomplete angle development, ischemia, and laser treatment, highlight the need for glaucoma screening in patients with ROP, both in the short and long term.

Choroidal Neovascularization and Macular Hemorrhage: Real-World Experience During the New York City COVID-19 Lockdown.

Purpose: This work reviews ocular, systemic, and demographic factors contributing to presentation of choroidal neovascular membrane (CNVM)-associated macular hemorrhage after the New York City coronavirus disease 2019 (COVID-19) lockdown. Methods: A retrospective, consecutive case series was conducted of all established patients presenting with macular hemorrhage between March 22, 2020, and August 10, 2020. Results: Fourteen patients (mean age 82.2 years) were evaluated. Ten patients had active CNVMs, 1 had an inactive lesion that was last injected 2 years prior, and 3 had new conversions from nonexudative age-related macular degeneration. In the actively treated CNVM group there was a delay in expected follow-up from 50.4 days to 125 days. Eight patients with previously active CNVM (73%) had a history of prior macular hemorrhage. Eight patients (57%) were on some form of antiplatelet or anticoagulation therapy. Twelve patients (86%) had COVID-19-specific risk factors besides age, and all but 1 patient (93%) delayed care without discussion with a physician. Ten patients (71%) had more than 1 week of symptoms prior to presentation. Twelve patients (86%) had signs of CNVM on prior optical coherence tomography. Conclusions: Adequate documentation of potential risks for hemorrhage (particularly prior hemorrhage or presence of subclinical type 1 CNVM), as well as COVID-19-specific risk factors, would aid triage of clinic appointments in future lockdowns. High-risk patients would likely benefit from direct physician communication discussing their individual risk profiles to alleviate anxiety over clinic visits and communicate their risk of severe vision loss.

Feasibility and Clinical Utility of Ultra-Widefield-Navigated Swept-Source Optical Coherence Tomography Imaging.

Purpose: This work aims to evaluate the clinical utility and feasibility of a novel scanning laser ophthalmoscope-based navigated ultra-widefield swept-source optical coherence tomography (UWF SS-OCT) imaging system. Methods: A retrospective, single-center, consecutive case series evaluated patients between September 2019 and October 2020 with UWF SS-OCT (modified Optos P200TxE, Optos PLC) as part of routine retinal care. The logistics of image acquisition, interpretability of images captured, nature of the peripheral abnormality, and clinical utility in management decisions were recorded. Results: Eighty-two eyes from 72 patients were included. Patients were aged 59.4 ± 17.1 years (range, 8-87 years). During imaging, 4.4 series of images were obtained in 4.1 minutes, with 86.4% of the image series deemed to be diagnostic of the peripheral pathology on blinded image review. The most common pathologic findings were chorioretinal scars (18 eyes). In 31 (38%) eyes, these images were meaningful in supporting clinical decision-making with definitive findings. Diagnoses imaged included retinal detachment combined with retinoschisis, retinal hole with overlying vitreous traction and subretinal fluid, vitreous inflammation overlying a peripheral scar, Coats disease, and peripheral retinal traction in sickle cell retinopathy. Conclusions: Navigated UWF SS-OCT imaging was clinically practical and provided high-quality characterization of peripheral retinal lesions for all eyes. Images directly contributed to management plans, including laser, injection or surgical treatment, for a clinically meaningful set of patients (38%). Future studies are needed to further assess the value of this imaging modality and its role in diagnosing, monitoring, and treating peripheral lesions.

Scleral-Sutured Intraocular Lens Dislocations Secondary to Eyelet Fractures.

OBJECTIVE: To report clinical features and visual outcomes following eyelet fractures of scleral-sutured enVista MX60 (Bausch + Lomb) intraocular lenses (IOL). DESIGN: Retrospective, multi-center, multi-surgeon, observational case series. METHODS: Study Population: Patients with scleral-sutured enVista MX60 IOLs that experienced either an intraoperative or post-operative eyelet fracture associated with dislocation or subluxation. PROCEDURES: All records were reviewed for patients with a dislocated or subluxed scleral-sutured enVista MX60 IOL. Clinical features and outcomes were gathered. Main Outcome Measures: Clinical setting, surgical technique, complications, and visual acuity. RESULTS: A total of 25 scleral-sutured enVista MX60 IOLs displacements secondary to eyelet fractures in 23 eyes of 23 patients were included. There were 20 IOLs that sustained a postoperative fracture and 5 IOLs that sustained an intraoperative fracture. Of the postoperative fractures, 7 were dislocated and 13 were subluxed. Gore-Tex was the suture of choice for 19 of the postoperative fractures and all 5 of the intraoperative fractures, and Prolene was used for 1 postoperative fracture. The mean time until postoperative fracture was 96 ± 125 days, and the median time was 61 (IQR 48-144) days. Of the postoperative fractures, new MX60s were sutured in 10 patients, and 2 of them experienced repeat displacements due to a new eyelet fracture. In the intraoperative fracture group, new MX60s were sutured in 4 patients and an Akreos AO60 lens was placed in the 5th patient. The mean preoperative best-corrected logMAR visual acuity for all patients improved from 1.2 ± 0.8 (20/317 Snellen equivalent) to 0.5 ± 0.5 (20/63 Snellen equivalent) at most recent follow-up after lens replacement. CONCLUSIONS: Scleral-sutured MX60 intraocular lenses can experience intraoperative or postoperative eyelet fractures, resulting in lens subluxation or dislocation. Surgeons should be aware of this complication when evaluating secondary intraocular lens options.

Fractal Dimension Analysis of Widefield Choroidal Vasculature as Predictor of Stage of Macular Degeneration.

Purpose: To evaluate the fractal dimension (Df ) of the choroidal vasculature using widefield indocyanine green (ICG) angiography and correlate it with the stage of age-related macular degeneration (AMD). Methods: Widefield ICG angiography performed on 38 eyes was retrospectively analyzed using the FracLac application within the National Institutes of Health ImageJ software to determine regional fractal dimensions in the macular field and widefield. These values were then associated with a diagnosis of no AMD, non-exudative AMD (subdivided into early/intermediate stage vs. advanced stage), or exudative AMD (subdivided into with or without geographic atrophy). The mean values were compared using Wilcoxon's test. Results: Early/intermediate non-exudative AMD and exudative AMD without geographic atrophy were found to have statistically significantly lower Df values compared to an absence of AMD when examining the macular field. Exudative AMD with geographic atrophy was found to have a statistically significant lower choroidal fractal dimension compared to no AMD when studied in the widefield. Conclusions: Advanced stages of macular degeneration were found to have significantly decreased the fractal dimensions of choroidal vasculature on widefield ICG compared to early/intermediate stages, possibly implying a generalized reduction in complexity and/or vessel caliber of the choroid with advancing stage of AMD. This finding agrees with previous understanding of the development of choriocapillaris atrophy in advanced macular degeneration. Translational Relevance: These findings suggest that using automated fractal analysis techniques can aid in differentiating stages of macular degeneration and, with further study, may be used to predict advancement of macular degeneration.

Hypopyon following selective laser trabeculoplasty.

PURPOSE: To report a hypopyon following selective laser trabeculoplasty (SLT). OBSERVATIONS: An 85-year-old woman with primary open-angle glaucoma underwent routine SLT. In the early post-procedural period, she presented with pain and decreased vision, and she was found to have hypopyon, trabeculitis, and corneal edema. The patient was treated with prednisolone acetate and empirically with valacyclovir due to the possibility of herpetic keratouveitis. Work-up for potential etiologies was unrevealing. Her symptoms resolved with treatment, and at eight months follow-up her visual acuity and intraocular pressure had stabilized to her baseline. CONCLUSIONS: Though safe, SLT may be associated with rare adverse events requiring intervention. Hypopyon following SLT is extremely rare, and investigation for causes unrelated to the history of SLT should be undertaken as appropriate. IMPORTANCE: To the best of our knowledge, this is the first report of a hypopyon following SLT in a patient with no history of inflammatory intra-ocular disease.

Symmetric Age Association of Retinal Degeneration in Patients with CLN2-Associated Batten Disease.

PURPOSE: Mutations in the CLN2 gene lead to a neurodegenerative and blinding lysosomal storage disorder: late infantile neuronal ceroid lipofucinosis, also known as "CLN2 disease." The purpose of the current study was to characterize the evolution of CLN2-associated retinal manifestations using the Weill Cornell Batten Scale (WCBS) and the age association of the retinal degeneration using central subfield thickness (CST) measurements and then correlate these findings with fundus photography and OCT to determine a critical period for retinal intervention. DESIGN: Retrospective, single-center cohort. PARTICIPANTS: Eighty-four eyes of 42 treatment-naïve patients with CLN2 disease. METHODS: Clinical records, fundus photographs, and OCT imaging for patients with CLN2 disease collected during examinations under anesthesia were reviewed. Imaging was categorized per WCBS criteria by 3 masked graders. MAIN OUTCOME MEASURES: CLN2-associated retinopathy assessed using WCBS scores, fundus photographs, and OCT imaging, correlated with patient age. RESULTS: Eighty-four eyes of 42 patients had baseline fundus photographs, with baseline OCT in 31 eyes of 16 patients. Fundus photographs were obtained serially for 26 eyes of 13 patients, and serial OCT scans were obtained in 10 eyes of 5 patients. At baseline, bilateral WCBS scores were highly correlated for OCT and fundus photographs (r = 0.96 and 0.82, respectively). Central subfield thickness was negatively correlated with left and right eye WCBS OCT scores (r = -0.92 and -0.83, respectively; P < 0.001) and fundus photograph scores (r = -0.80 and -0.83, respectively; P < 0.001). OCT thickness was symmetrical between each eye. Baseline OCT data with age fit using a sigmoid function demonstrated a period of accelerated loss between 48 and 72 months of age. CONCLUSIONS: Retinal degeneration associated with CLN2 disease manifests as a progressive, symmetrical decline, which appears to accelerate during a critical period at 48 to 72 months of age, suggesting intervention with retina-specific CLN2 gene therapy should occur ideally before or as early as possible within this critical period. The WCBS is a valuable tool and is highly correlated with the extent of retinal degeneration observed in OCT or fundus photographs; by using the fellow eye as a control, this grading scale can be used to monitor the effect of CLN2 gene therapy in future trials.

Viscostretch: A Novel Surgical Technique for Refractory Macular Holes.

Purpose: We present a novel technique of subretinal viscodissection for addressing refractory macular holes (MHs). Methods: A case report and surgical technique description are provided. Results: In this technique, standard pars plana vitrectomy with internal limiting membrane peeling (unless previously peeled) is performed. A cohesive ophthalmic viscosurgical device (OVD) is injected through the MH, focally detaching the parafoveal retinal tissue around the hole. The OVD is removed at the conclusion of the air-fluid exchange. We provide an example of a recurrent 833-µm MH that was successfully closed despite failing initial surgery. There was no retention of subretinal OVD, and anatomic closure was achieved in this patient with a refractory MH. Conclusions: In refractory holes with adhesions at the MH base, this technique mobilizes the adjacent retinal tissue and uses the air's surface tension to facilitate closure. Surgeons can consider using this technique as part of their MH arsenal.

Focal Choroidal Excavation Expansion Following Treatment of Associated Choroidal Neovascular Membrane.

The authors describe a case of a previously unreported phenomenon of focal choroidal excavation (FCE) expansion, in absence of inflammation, due to treatment of an associated choroidal neovascular membrane (CNVM). A patient with new type 2 CNVM, treated during 43 months of follow-up with aflibercept, experienced significant expansion of an FCE with conversion from nonconforming to conforming type. FCE is part of the pachychoroid spectrum and the regression of an associated CNVM during aflibercept treatment as seen in the authors' patient may elucidate the pathogenesis of some forms of focal choroidal excavation and their evolution over time. [Ophthalmic Surg Lasers Imaging Retina. 2020;51:54-57.].

Corneal hysteresis and anterior segment optical coherence tomography anatomical parameters in primary angle closure suspects.

IMPORTANCE: Corneal hysteresis (CH) is a dynamic marker of structural and functional changes in the cornea associated with intraocular pressure (IOP) and central corneal thickness, but its utility in assessing primary angle closure suspects (PACS) has not been fully elucidated. BACKGROUND: This study assesses if anterior segment measurements correlate with CH in PACS patients. DESIGN: IRB-approved retrospective review of imaging and records at a university practice. PARTICIPANTS: Sixty-three eyes from 37 patients diagnosed as PACS, without other ocular pathology. METHODS: Every eye underwent measurements including: ocular response analyzer (ORA), anterior segment optical coherence tomography (OCT) and a clinical evaluation. ORA measurements were correlated with other anatomic parameters using a mixed effects multivariable linear regression framework. MAIN OUTCOME MEASURES: ORA measurements included: CH, corneal resistance factor, Goldmann IOP (IOPg ) and corneal compensated IOP (IOPcc ). Anterior segment OCT measurements included: central corneal thickness (CCTOCT ), nasal and temporal peripheral corneal thicknesses (PCT1 and PCT2), anterior chamber depth (ACD), nasal angle to temporal angle distance (ATA) and temporal and nasal angle measurements. Clinical measurements included: central corneal thickness via pachymetry, IOP measured by Goldmann applanation, axial length by A-scan ultrasound and spherical equivalent. RESULTS: CH was negatively correlated with IOPcc, and ACD CH was positively correlated with CCTOCT , CCTp , CRF, PCT1 and PCT2. Females were found to have lower CH. In multivariable regression controlling for gender, CCT, PCT, IOP and ACD, no correlation was seen between CH and anatomic measurements. CONCLUSIONS AND RELEVANCE: CH values in PACS do not correlate with anterior segment anatomy.

Delayed bilateral fibrinous anterior chamber reaction following autologous bone marrow transplant and cataract surgery.

PURPOSE: Immune reconstitution uveitis (IRU) is a well-described phenomenon that by definition occurs in patients with AIDS who undergo highly active antiretroviral therapy resulting in a rebound inflammatory response to the presence of clinically latent cytomegalovirus (CMV). We hypothesize that similar phenomena may exist in other cohorts who undergo transient immunosuppression with rapid white blood cell count recovery. OBSERVATIONS: A patient developed rebound inflammation a few months after cataract surgery with intraocular lens placement characterized by photophobia, significant anterior chamber cell and fibrinous deposits. She had a history of multiple myeloma treated with chemotherapy and a recovery of white blood cell counts following autologous bone marrow transplant. She underwent a thorough work-up for infectious etiologies, as well as the presence of intraocular CMV, which were negative. Her vision and symptoms improved to baseline with the use of topical steroids and at one year her exam remained stable. CONCLUSIONS AND IMPORTANCE: With a negative work-up for infectious etiologies, and the timing and clinical presentation, the patient's inflammation was likely the result of rapid white blood cell count recovery following iatrogenic immunosuppression similar to the mechanism described for IRU.