Proliferative Sickle Cell Retinopathy: Outcomes of Vitreoretinal Surgery.

PURPOSE: To report the clinical presentation and outcomes in patients who underwent surgery for proliferative sickle cell retinopathy (PSCR). DESIGN: Retrospective, consecutive case series. SUBJECTS: All patients who underwent vitreoretinal surgery for complications secondary to PSCR between January 1, 2014, and December 31, 2021, at a university referral center. METHODS: Retrospective consecutive case series. MAIN OUTCOME MEASURES: Best-corrected visual acuity (BCVA), single operation anatomic success rate. RESULTS: The study included 65 eyes of 61 patients. Disease distribution included 24 (44.4%) eyes with hemoglobin SC disease, 14 (25.9%) with hemoglobin SS disease, 13 (24.1%) with sickle cell trait, and 3 (5.6%) with sickle cell-ß thalassemia. Preoperative transfusion was not performed in any study patients. Regional anesthesia with monitored anesthesia care (RA-MAC) was utilized in 58 (89.2%) eyes and general anesthesia in 7 (10.8%). In eyes that underwent surgery for retinal detachment (RD; N = 52) the rate of single operation anatomic success was 72.4% with combined scleral buckling/pars plana vitrectomy (SB/PPV; N = 29) compared with 47.8% with PPV alone (N = 23; P = 0.07). Mean BCVA at the last follow-up examination was 1.27 (20/372) in the SB/PPV group and 1.05 (20/226) in the PPV group (P = 0.48). In all SB cases, an encircling band was utilized and there were no known cases of anterior segment ischemia. All eyes that had surgery for vitreous hemorrhage (N = 13) underwent PPV with endolaser and mean BCVA improved from 1.67 (20/944) preoperatively to 0.45 (20/56) at last follow-up examination (P < 0.001). Mean preoperative BCVA, indication for surgery, single operation success rate, and mean BCVA at last follow-up examination did not differ based on sickle cell disease type (P > 0.05). CONCLUSIONS: In patients with RD, SB/PPV achieved slightly higher rates of single operation anatomic success compared with PPV alone. Visual acuity outcomes were similar in the 2 groups. The majority of patients received RA-MAC anesthesia and preoperative transfusions were not performed. There were no cases of postoperative anterior segment ischemia. Hemoglobin SC disease was the most common disease type in the current study and surgical outcomes did not differ between sickle cell disease types. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Choroideremia presenting as vision loss secondary to choroidal neovascularization.

BACKGROUND: Choroidal neovascularization (CNV) is a rare complication of choroideremia that occurs secondary to relative atrophy of the retinal pigment epithelium and eventual rupture of Bruch's membrane. The ideal management of CNV in choroideremia is unclear. MATERIALS AND METHODS: Case report. OBSERVATIONS: A 14-year-old male with no known ocular history presented to the eye emergency department complaining of a central scotoma in the right eye for 4 days. He had no past medical history and family history was unremarkable for known ocular disease. Visual acuity was 20/70 in the right eye and 20/30 in the left eye. Posterior segment exam revealed chorioretinal atrophy extending from the outer macula to the midperiphery in both eyes. There was CNV with associated subretinal hemorrhage in the right eye. Optical coherence tomography demonstrated the presence of CNV with subretinal fluid in the right eye and parafoveal outer retinal atrophy in both eyes. Genetic testing revealed a hemizygous exon 2 deletion on the CHM gene, pathogenic for choroideremia. The patient received a total of 3 injections 4 weeks apart followed by 1 injection 6 weeks later with resolution of the subretinal hemorrhage and reduction in CNV size with improvement in visual acuity to 20/20 at last follow-up exam. CONCLUSIONS AND IMPORTANCE: Choroidal neovascularization is a rare cause of central vision loss in patients with choroideremia. In this report, we demonstrate a good functional and anatomic response to intravitreal bevacizumab in a 14-year-old patient with undiagnosed choroideremia who presented with CNV-induced central vision loss.

Retinal Detachment Associated with Retinal Dialysis: Clinical Features and Outcomes of Surgery in a 10-Year Study.

PURPOSE: To report the surgical approaches and outcomes in patients undergoing surgery for retinal detachment associated with retinal dialysis. DESIGN: Retrospective, consecutive case series. SUBJECTS: All patients who underwent surgery for retinal detachment secondary to retinal dialysis between January 1, 2012, and January 1, 2022. METHODS: Retrospective consecutive case series. MAIN OUTCOME MEASURES: Best-corrected visual acuity (BCVA), single-operation success rate. RESULTS: The study cohort included 60 eyes of 58 patients with a mean age of 26.4 (standard deviation, 13.0) years. Males comprised 49 (84.5%) patients. Known trauma occurred in 35 (61.4%) cases. Initial surgical management included scleral buckling (SB) in 49 (81.7%) eyes and combined SB and pars plana vitrectomy (PPV) in 11 (18.3%) eyes. Preoperative BCVA correlated with BCVA at last follow-up visit (r = 0.66; P < 0.001). At last visit, the SB group had a mean logarithm of the minimum angle of resolution BCVA of 0.36 (20/46) and a single-operation success rate of 76.9% at 6 months, whereas the SB/PPV group had a mean logarithm of the minimum angle of resolution BCVA of 1.08 (20/238) and single-operation success rate of 77.8% (P = 0.04 and P = 0.96, respectively). Six eyes in the SB/PPV group received silicone oil tamponade. In eyes with at least 1 year of follow-up, 4 (14.8%) in the SB group and 6 (100%) in the SB/PPV group developed a visually significant cataract requiring cataract surgery (P < 0.001). CONCLUSIONS: Retinal detachment associated with retinal dialysis is typically associated with trauma and more often occurs in young male patients. The current study confirms that SB without PPV is an effective initial treatment strategy for most patients with retinal dialysis and has a low rate of cataract formation. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Stem cell-derived retinal pigment epithelium cell therapy: Past and future directions.

The eyes are relatively immune privileged organs, making them ideal targets for stem cell therapy. Researchers have recently developed and described straightforward protocols for differentiating embryonic and induced pluripotent stem cells into retinal pigment epithelium (RPE), making diseases affecting the RPE, such as age-related macular degeneration (AMD), viable targets for stem cell therapy. With the advent of optical coherence tomography, microperimetry, and various other diagnostic technologies, the ability to document disease progression and monitor response to treatments such as stem cell therapy has been significantly enhanced in recent years. Previous phase I/II clinical trials have employed various cell origins, transplant methods, and surgical techniques to identify safe and efficacious methods of RPE transplantation, and many more are currently underway. Indeed, findings from these studies have been promising and future carefully devised clinical trials will continue to enhance our understanding of the most effective methods of RPE-based stem cell therapy, with the hope to eventually identify treatments for disabling and currently incurable retinal diseases. The purpose of this review is to briefly outline existing outcomes from initial clinical trials, review recent developments, and discuss future directions of clinical research involving stem-cell derived RPE cell transplantation for retinal disease.

VALSALVA RETINOPATHY: Clinical Features and Treatment Outcomes.

PURPOSE: To report the clinical presentation and outcomes in patients with Valsalva retinopathy. METHODS: This was a retrospective case series of patients diagnosed with Valsalva retinopathy between June 1, 2010, and May 31, 2020. Clinical notes, operative reports, fundus photography, and optical coherence tomography images were reviewed. RESULTS: This study comprised 58 eyes of 58 patients. The most common causes were lifting (34.4%), vomiting (20.6%), straining (20.6%), and coughing (17.2%). Mean best-corrected visual acuity at diagnosis was 20/163. The most frequently involved vitreoretinal compartment was the subhyaloid space (42.3%) followed by the intraretinal (32.7%), intravitreal (23.1%), and subretinal (13.4%) spaces. Mean best-corrected visual acuity of all patients was 20/59 at 3 months, 20/48 at 6 months, and 20/22 at 1 year. Mean time to clearance of hemorrhage on clinical examination was 99.0 ± 18.7 days in patients who underwent observation and 4.5 ± 3.5 days after surgery in patients who received pars plana vitrectomy. CONCLUSION: Valsalva retinopathy is generally associated with a favorable visual prognosis. Most eyes perform well with observation although pars plana vitrectomy may be indicated in patients requiring rapid resolution of hemorrhage.

Outcomes of Pars Plana Vitrectomy with Panretinal Photocoagulation for Treatment of Proliferative Diabetic Retinopathy Without Retinal Detachment: A Seven-Year Retrospective Study.

Objective: To review clinical outcomes of patients with proliferative diabetic retinopathy (PDR) and vitreous hemorrhage (VH) who underwent pars plana vitrectomy (PPV) with endolaser panretinal photocoagulation (PRP) without retinal detachment (RD) repair. Methods: Retrospective chart review of the rate of postoperative clinical findings and visual acuity in patients with PDR from May 2014 to August 2021. Results: Pars plana vitrectomy with endolaser PRP was performed in 81 eyes of 81 patients (mean age of 62.1 ± 10.5 years). At a median follow-up of 18 months, mean Snellen best-corrected visual acuity (BCVA) significantly improved from 20/774 preoperatively to 20/53 at last follow-up (P < 0.001). Postoperative complications and clinical findings included VH (12.3%), diabetic macular edema (DME) (12.3%), ocular hypertension (8.6%), RD (4.9%), and need for additional PPV (6.2%). Eyes with PRP performed within 6 months before surgery had a lower frequency of developing postoperative VH (5.3%) compared to eyes that received PRP more than 6 months before surgery (27.3%, P = 0.04). Eyes that received preoperative anti-vascular endothelial growth factor (VEGF) treatment (2.0%) had a lower frequency of postoperative VH compared to eyes that did not receive anti-VEGF treatment (14.3%, P = 0.04). Eyes that received intraoperative sub-tenon triamcinolone acetonide developed postoperative DME (4.0%) less frequently than eyes that did not receive sub-tenon triamcinolone acetonide (26.7%, P = 0.04). Conclusion: In patients with PDR and VH, PPV with PRP yielded significant improvements in visual acuity and resulted in overall low rates of recurrent postoperative VH. Preoperative anti-VEGF and PRP laser treatment were associated with lower rates of postoperative VH. Furthermore, intraoperative use of sub-tenon triamcinolone acetonide was associated with a lower rate of postoperative DME. Pars plana vitrectomy with endolaser PRP in conjunction with the aforementioned pre- and intraoperative therapies is an effective treatment for patients with PDR and VH.

Pars Plana Vitrectomy for Retained Lens Fragments After Cataract Surgery: Outcomes Based on Timing of Surgery.

Purpose: To evaluate the outcomes and complications in patients with retained lens fragments (RLF) after cataract surgery, comparing those who received pars plana vitrectomy (PPV) on the same day, within 1 week, or later than 1 week after cataract surgery. Patients and Methods: Retrospective case series of all patients who underwent PPV for RLF at Bascom Palmer Eye Institute between January 1, 2012 and September 30, 2020. Individuals with less than 3 months of follow-up, chronic uveitis, congenital cataract, previtrectomy retinal detachment (RD), and severe trauma were excluded. All analyses for categorical and binary variables used chi-squared tests. Analyses for continuous variables were performed using multivariate analyses of covariance, adjusting for differences in baseline visual acuity before cataract surgery. Results: The study included 246 eyes of 246 patients. The timing distribution included the following: 140 (57%) eyes underwent same-day PPV, 33 (13%) eyes underwent same-week PPV, and 73 (30%) eyes underwent PPV after 1 week (up to 90 days). When all eyes were included in analysis, there were no statistically significant differences in mean best-corrected visual acuity (BCVA) between groups at last follow-up examination (P = 0.07). When only eyes without known pre-existing ocular disease (N = 157) were included in analysis, there were no differences in mean BCVA between groups at all postoperative timepoints (P > 0.05). The rate of RD did not differ between groups when eyes with and without pre-existing ocular disease were analyzed (P > 0.05). Conclusion: In the current study, there were no statistically significant differences in postoperative BCVA or rates of RD at last follow-up examination in eyes undergoing PPV for RLF on the same day, within 1 week, or later than 1 week after cataract surgery.

Novel Machine-Learning Based Framework Using Electroretinography Data for the Detection of Early-Stage Glaucoma.

Purpose: Early-stage glaucoma diagnosis has been a challenging problem in ophthalmology. The current state-of-the-art glaucoma diagnosis techniques do not completely leverage the functional measures' such as electroretinogram's immense potential; instead, focus is on structural measures like optical coherence tomography. The current study aims to take a foundational step toward the development of a novel and reliable predictive framework for early detection of glaucoma using machine-learning-based algorithm capable of leveraging medically relevant information that ERG signals contain. Methods: ERG signals from 60 eyes of DBA/2 mice were grouped for binary classification based on age. The signals were also grouped based on intraocular pressure (IOP) for multiclass classification. Statistical and wavelet-based features were engineered and extracted. Important predictors (ERG tests and features) were determined, and the performance of five machine learning-based methods were evaluated. Results: Random forest (bagged trees) ensemble classifier provided the best performance in both binary and multiclass classification of ERG signals. An accuracy of 91.7 and 80% was achieved for binary and multiclass classification, respectively, suggesting that machine-learning-based models can detect subtle changes in ERG signals if trained using advanced features such as those based on wavelet analyses. Conclusions: The present study describes a novel, machine-learning-based method to analyze ERG signals providing additional information that may be used to detect early-stage glaucoma. Based on promising performance metrics obtained using the proposed machine-learning-based framework leveraging an established ERG data set, we conclude that the novel framework allows for detection of functional deficits of early/various stages of glaucoma in mice.

EVALUATION OF RETINAL DISPLACEMENT FOLLOWING PRIMARY SCLERAL BUCKLING FOR MACULA-INVOLVING RHEGMATOGENOUS RETINAL DETACHMENT.

PURPOSE: To evaluate the incidence and degree of retinal displacement following scleral buckling surgery for macula-involving rhegmatogenous retinal detachment. METHODS: Retrospective interventional case series comprised of patients treated with primary scleral buckling procedure without gas tamponade for macula-involving rhegmatogenous retinal detachment and imaged postoperatively with fundus autofluorescence imaging between June 1, 2016 and July 25, 2021. Clinical notes, operative reports, fundus autofluorescence photographs, and optical coherence tomography images were reviewed. The presence and degree of retinal displacement were recorded. RESULTS: Twelve eyes of 11 patients were included. One (8%) eye with an epiretinal membrane demonstrated 0.1 mm of retinal displacement along the superior arcade and in the superotemporal periphery. The remainder of eyes (92%) did not show any identifiable signs of retinal displacement. CONCLUSION: Retinal displacement does not seem to be a frequent complication of primary scleral buckling surgery for macula-involving rhegmatogenous retinal detachment.

Ocular manifestations of Beckwith-Wiedemann syndrome.

Beckwith-Wiedemann syndrome (BWS; OMIM #130650) is a pediatric overgrowth disorder with few known ocular manifestations. We retrospectively reviewed the medical records of patients with BWS evaluated at Bascom Palmer Eye Institute over a 10-year period and identified 5 patients, of whom 4 presented with ocular misalignment and 1 with eye rubbing. Three patients were noted to have strabismus, and 1 patient manifested with significant astigmatism. No patients received surgical intervention.

Agrobacterium radiobacter Endophthalmitis Associated with Baerveldt Tube Exposure.

Agrobacterium radiobacter is a Gram-negative bacillus and a rare cause of endophthalmitis. An 85-year-male presented with late-onset endophthalmitis associated with exposure of an inferonasal Baerveldt tube. The patient was initially treated with anterior chamber paracentesis and intravitreal antibiotics. Aqueous humor culture revealed A. radiobacter resistant to cefazolin, ceftazidime, amikacin, tobramycin, and trimethoprim-sulfamethoxazole. Subsequently, the patient underwent explantation of the glaucoma drainage implant (GDI). After initial improvement, the patient had clinical worsening and was diagnosed with recurrence. Subsequent treatment involved explantation of the second GDI in addition to pars plana vitrectomy with silicone oil infusion, intraocular lens removal, and administration of intravitreal antibiotics. Visual acuity improved but remained at count fingers at 2 weeks. This is the first reported patient with A. radiobacter endophthalmitis associated with an exposed GDI. This report illustrates the resistant nature of this organism in addition to the efficacy of silicone oil administration and intraocular prosthesis explantation.

The Contribution of Anterior Segment Abnormalities to Changes in Intraocular Pressure in the DBA/2J Mouse Model of Glaucoma: DBA/2J-Gpnmb +/SjJ Mice as Critical Controls.

The contributions of anterior segment abnormalities to the development of ocular hypertension was determined in the DBA/2J mouse model of glaucoma. Intraocular pressure (IOP) was measured non-invasively. Iris pigment dispersion (IPD) and corneal calcification were measured weekly starting at 20 weeks of age in DBA/2J and DBA/2J-Gpnmb +/SjJ mice. Thickness, surface area, auto-fluorescence intensity, and perimeter length of calcified regions were measured in postmortem corneas using confocal microscopy. DBA/2J mice developed elevated IOP between 9 and 12 months of age, but DBA/2J-Gpnmb +/SjJ mice did not. Corneal calcification was found at all ages observed and at similar frequencies in both strains with 83.3% of DBA/2J eyes and 60.0% of DBA/2J-Gpnmb +/SjJ eyes affected at 12 months (P = 0.11). Calcification increased with age in both DBA/2J (P = 0.049) and DBA/2J-Gpnmb +/SjJ mice (P = 0.04) when assessed qualitatively and based on mixed-effects analysis. No differences in the four objective measures of calcification were observed between strains or ages. At 12 months of age, DBA/2J mice with corneal calcification had greater mean IOP than DBA/2J mice without corneal calcification. IOP was not correlated with the qualitatively assessed measures of calcification. For the subset of eyes with ocular hypertension, which were only found in DBA/2J mice, IOP was negatively correlated with the qualitative degree of calcification, but was not correlated with the four quantitative measures of calcification. Differences in IOP were not observed between DBA/2J-Gpnmb +/SjJ mice with and without calcification at any age. IPD increased with age and demonstrated a moderate correlation with IOP in DBA/2J mice, but was not observed in DBA/2J-Gpnmb +/SjJ mice. In the DBA/2J mouse model of glaucoma, increased IPD is positively correlated with an increase in IOP and corneal calcification is present in the majority of eyes at and after age 9 months. However, while IPD causes ocular hypertension, corneal calcification does not appear to contribute to the elevation of IOP, as the control strain DBA/2J-Gpnmb +/SjJ exhibits corneal calcification similar to DBA/2J mice, but does not develop ocular hypertension. Corneal calcification, therefore, does not appear to be a contributing factor to the development of elevated IOP in DBA/2J mice.

Microperimetry as a diagnostic tool for the detection of early, subclinical retinal damage and visual impairment in multiple sclerosis.

BACKGROUND: A majority of multiple sclerosis patients experience visual impairment, often as the initial presenting symptom of the disease. While structural changes in the retinal nerve fiber layer and optic nerve have demonstrated correlations with brain atrophy in multiple sclerosis using magnetic resonance imaging, a non-invasive, cost-effective, and clinically efficacious modality to identify early damage and facilitate prompt therapeutic intervention to slow the progression of multiple sclerosis and its ocular manifestations, is still urgently needed. In this study, we sought to determine the role of macular sensitivity measured by microperimetry in the detection of subclinical multiple sclerosis-related retinal damage and visual dysfunction. METHODS: This cross-sectional observational case-control study involved population-based samples of multiple sclerosis patients and age-, race-, and gender-matched healthy control subjects. Among the key criteria for the multiple sclerosis patients were diagnosis by the McDonald criteria, visual acuity greater than 20/25, and no history of optic neuritis. Macular sensitivity and average macular thickness were measured in all subjects using microperimetry and spectral-domain optical coherence tomography, respectively. Pearson correlation coefficients were measured using bivariate correlations. Sample means, mean differences, and 95% confidence intervals were calculated using independent sample t-tests. RESULTS: Twenty-eight eyes from 14 MS patients and 18 eyes from 9 control subjects were included. Mean macular sensitivity of control subjects and multiple sclerosis patients in decibels was 18.2 ± 0.4 and 16.5 ± 0.4, respectively, corresponding to a mean difference of 1.7 (95% CI, 1.1-2.4; P < 0.001). Macular sensitivity was positively correlated with macular thickness in multiple sclerosis patients (r = 0.49, P = 0.01) but not control subjects (r = 0.15, P = 0.55). CONCLUSIONS: Macular sensitivity as measured by microperimetry was decreased in multiple sclerosis patients with normal visual acuity and no history of optic neuritis. Furthermore, macular sensitivity demonstrated a positive correlation with macular thickness as measured by optical coherence tomography. As such, microperimetry may represent a non-invasive and efficient method to identify signs of subclinical visual dysfunction that correspond with early macular architectural changes characteristic of multiple sclerosis.

Endophthalmitis Caused by Agrobacterium radiobacter following Intravitreal Aflibercept for Diabetic Retinopathy.

Agrobacterium (Rhizobium) radiobacter is a gram-negative bacillus rarely implicated in ocular disease. A 79-year-old male who performed extensive yardwork following intravitreal injection with aflibercept for diabetic macular edema developed endophthalmitis caused by Agrobacterium radiobacter on post-injection day 7. The patient was treated with vitreous tap and intravitreal injection of vancomycin and ceftazidime with clearance of the infection and restoration of his baseline visual acuity at 20/80.

Cavernous sinus thrombosis caused by Streptococcus constellatus-associated Lemierre syndrome presenting as an isolated abducens nerve palsy.

PURPOSE: To describe a patient with Streptococcus constellatus-associated Lemierre syndrome complicated by eventual cavernous sinus thrombosis (CST) that manifested as an isolated abducens nerve palsy. OBSERVATIONS: A patient with a history of heavy alcohol use presented with Lemierre syndrome caused by an odontogenic infection due to Streptococcus constellatus. Despite initiation of intravenous antibiotics and eventual eradication of her bacteremia, she developed an isolated abducens nerve palsy on hospital day 7 due to associated CST. CONCLUSIONS AND IMPORTANCE: CST is a rare complication of odontogenic infection and Lemierre syndrome. This case demonstrates the potential for primary odontogenic infections to progress to life- and sight-threatening diseases. This case also illustrates the importance of considering uncommon pathogens as the etiology of CST based on the suspected source of primary infection.

Post-Traumatic Endophthalmitis Caused by Oerskovia turbata.

PURPOSE: To present a previously unreported cause of bacterial endophthalmitis manifesting as delayed post-traumatic endophthalmitis ultimately responsive to total capsulectomy. CASE REPORT: A patient presented with chronic endophthalmitis that occurred after ocular trauma with organic material and Oerskovia turbata was eventually isolated. After a prolonged treatment course, including two pars plana vitrectomies and total capsulectomy, the patient achieved 20/80 visual acuity at 1-year follow-up. CONCLUSION: This is the first reported patient with endophthalmitis due to O. turbata, a Gram-positive bacillus found in soil that rarely causes human infection. The infection had a delayed presentation despite early prophylactic antibiotics and was ultimately eliminated with total capsulectomy. Removal of lens and lens capsule may be necessary in the management of post-traumatic endophthalmitis unresponsive to more conservative therapy, particularly in cases involving atypical organisms and lens capsule violation.

Reactive Oxygen Species-Mediated Damage of Retinal Neurons: Drug Development Targets for Therapies of Chronic Neurodegeneration of the Retina.

The significance of oxidative stress in the development of chronic neurodegenerative diseases of the retina has become increasingly apparent in recent years. Reactive oxygen species (ROS) are free radicals produced at low levels as a result of normal cellular metabolism that are ultimately metabolized and detoxified by endogenous and exogenous mechanisms. In the presence of oxidative cellular stress, ROS are produced in excess, resulting in cellular injury and death and ultimately leading to tissue and organ dysfunction. Recent studies have investigated the role of excess ROS in the pathogenesis and development of chronic neurodegenerative diseases of the retina including glaucoma, diabetic retinopathy, and age-related macular degeneration. Findings from these studies are promising insofar as they provide clear rationales for innovative treatment and prevention strategies of these prevalent and disabling diseases where currently therapeutic options are limited. Here, we briefly outline recent developments that have contributed to our understanding of the role of ROS in the pathogenesis of chronic neurodegenerative diseases of the retina. We then examine and analyze the peer-reviewed evidence in support of ROS as targets for therapy development in the area of chronic neurodegeneration of the retina.