OUTCOMES OF INFECTIOUS PANUVEITIS ASSOCIATED WITH SIMULTANEOUS MULTI-POSITIVE OCULAR FLUID POLYMERASE CHAIN REACTION.

PURPOSE: To evaluate features of infectious panuveitis associated with multiple pathogens detected by ocular fluid sampling. METHODS: Single-center, retrospective, consecutive case series of patients with aqueous/vitreous polymerase chain reaction testing with >1 positive result in a single sample from 2001 to 2021. RESULTS: Of 1,588 polymerase chain reaction samples, 28 (1.76%) were positive for two pathogens. Most common pathogens were cytomegalovirus (n = 16, 57.1%) and Epstein-Barr virus (n = 13, 46.4%), followed by varicella zoster virus (n = 8, 28.6%), Toxoplasma gondii (n = 6, 21.4%), herpes simplex virus 2 (n = 6, 21.4%), herpes simplex virus 1 (n = 6, 21.4%), and Toxocara (n = 1, 3.6%). Mean initial and final visual acuity (logarithm of the minimum angle of resolution) were 1.3 ± 0.9 (Snellen ∼20/400) and 1.3 ± 1.1 (Snellen ∼20/400), respectively. Cytomegalovirus-positive eyes (n = 16, 61.5%) had a mean final visual acuity of 0.94 ± 1.1 (Snellen ∼20/175), whereas cytomegalovirus-negative eyes (n = 10, 38%) had a final visual acuity of 1.82 ± 1.0 (Snellen ∼20/1,320) ( P < 0.05). Main clinical features included intraocular inflammation (100%), retinal whitening (84.6%), immunosuppression (65.4%), retinal hemorrhage (38.5%), and retinal detachment (34.6%). CONCLUSION: Cytomegalovirus or Epstein-Barr virus were common unique pathogens identified in multi-PCR-positive samples. Most patients with co-infection were immunosuppressed with a high rate of retinal detachment and poor final visual acuity. Cytomegalovirus-positive eyes had better visual outcomes compared with cytomegalovirus-negative eyes.

Longitudinal quantification of choriocapillaris flow deficits in persistent placoid maculopathy: a case report.

BACKGROUND: Persistent placoid maculopathy (PPM) is a rare idiopathic chorioretinopathy characterized by choriocapillaris (CC) hypoperfusion. In a case of PPM, we quantified CC flow deficits (FDs) over time and observed an increase in CC perfusion as the visual acuity and outer photoreceptor anatomy improved. CASE PRESENTATION: A 58-year-old man was diagnosed with PPM in both eyes based on the patient's clinical presentation and imaging. He presented with sudden-onset central scotomas in both eyes for about two months. On referral, the best corrected visual acuity (BCVA) was 20/20 in the right eye and 20/100 in the left eye. Plaque-like yellowish macular lesions were observed bilaterally and autofluorescence imaging showed bilateral hyperautofluorescent lesions. Fluorescein angiography (FA) revealed early-phase hyper-fluorescent staining that intensified in the late phases, while indocyanine green angiography (ICGA) displayed persistent hypofluorescence in both eyes. Foveal centered swept source optical coherence tomography (SS-OCT) B-scans showed bilateral focal deposits on the level of retinal pigment epithelium (RPE) and disruption of outer photoreceptor bands. The CC FDs were quantified on SS-OCT angiography (SS-OCTA) images using a previously published algorithm that was validated. The CC FD% was 12.52% in the right eye and 14.64% in the left eye within a 5 mm circle centered on the fovea. After 5 months of steroid treatment, BCVA remained 20/20 in the right eye and improved to 20/25 in the left eye. On OCT imaging, the outer photoreceptor bands fully recovered in both eyes, while some focal deposits remained along the RPE in the left eye. The CC perfusion in both eyes improved, with CC FD% decreasing from 12.52% to 9.16% in the right eye and from 14.64% to 9.34% in the left eye. CONCLUSIONS: Significant impairment of macular CC perfusion was detected after the onset of PPM. Improvement in central macular CC perfusion corresponded with improvements in BCVA and outer retinal anatomy. Our findings suggest that imaging and quantification of CC FDs could serve as a valuable imaging strategy for diagnosing PPM and for following disease progression.

PENTOSAN POLYSULFATE SODIUM (ELMIRON) MACULOPATHY: A Genetic Perspective.

PURPOSE: To assess genetic associations for pentosan polysufate sodium maculopathy. METHODS: Genetic testing for inherited retinal dystrophy genes using exome testing and for 14 age-related macular degeneration-associated single nucleotide polymorphisms (SNPs) using panel testing were performed. In addition, full-field electroretinograms (ffERG) were obtained to identify any cone-rod dystrophy. RESULTS: Eleven of 15 patients were women, with a mean age of 69 (range 46-85). Inherited retinal dystrophy exome testing in five patients revealed six pathogenic variants, but failed to confirm inherited retinal dystrophy in any patient genetically. FfERG performed in 12 patients demonstrated only nonspecific a- and b-wave abnormalities in 11 cases and was normal in one case. For age-related macular degeneration single nucleotide polymorphisms, CFH rs3766405 ( P = 0.003) and CETP ( P = 0.027) were found to be statistically significantly associated with pentosan polysulfate maculopathy phenotype compared with the control population. CONCLUSION: Pentosan polysulfate maculopathy is not associated with Mendelian inherited retinal dystrophy genes. However, several age-related macular degeneration risk alleles were identified to be associated with maculopathy compared with their frequency in the normal population. This suggests a role for genes in disease pathology, particularly the alternative complement pathway. These findings would benefit from further investigation to understand the risk of developing maculopathy in taking pentosan polysulfate.

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.

Comparison of Unilateral and Bilateral Surgical Approaches for the Treatment of Age-Related Divergence Insufficiency Esotropia.

PURPOSE: Age-related divergence insufficiency-esotropia (ARDIE) is characterized by greater esodeviation at distance than near. This study aims to compare the outcomes of unilateral and bilateral surgical approaches. PATIENTS AND METHODS: Sixty-two cases treated at the Kellogg Eye Center, the University of Michigan, from 1995 to 2018 were retrospectively reviewed. One surgeon used unilateral procedures including unilateral medial rectus recession (n = 24, group 1) or unilateral recession-resection (n = 18, group 2) with an adjustable suture. Another surgeon used bilateral medial rectus recession with fixed sutures (n = 20, group 3). RESULTS: For patients with distance esodeviation <15∆, postoperative distance deviations in both group 1 and group 3 were not statistically different (p = .352). For patients with esodeviations 15-20∆, postoperative distance deviations in all 3 groups were also not statistically different (p = .142). Similarly, patients with deviations >20∆ did not show significantly different postoperative distance alignment (p = .082) between group 2 and 3. Overall, group 2 had the highest overall success rate (90%) (mean at distance = 1.17∆ exodeviation, at near = 2.33∆ exodeviation). CONCLUSION: Both unilateral medial rectus recession ± lateral rectus resection and bilateral medial rectus recession surgical approaches produced similar favorable outcomes in ARDIE.

Surgical Outcomes of Acute Retinal Necrosis-Related Retinal Detachment in Polymerase Chain Reaction-Positive Patients: A Single-Center Experience.

PURPOSE: To evaluate the clinical features, operative techniques, and surgical outcomes of patients who underwent surgery for acute retinal necrosis (ARN)-related retinal detachment (RD). DESIGN: Retrospective, longitudinal, consecutive case series. PARTICIPANTS: Patients with polymerase chain reaction-positive ARN presenting from 2011 to 2021 who underwent vitreoretinal surgery for ARN-related RD at our institution. METHODS: Univariate, multivariate, and survival analyses were used to determine predictors of anatomic and functional outcomes. MAIN OUTCOME MEASURES: Single-surgery anatomic success rate, recurrent RD, and visual acuity (VA) at 1 year. RESULTS: Thirty-four eyes of 34 patients (32.4% women, mean age, 45.1 ± 20.4 years) were included for analysis with a median follow-up of 2.5 years (interquartile range [IQR], 0.8-5.5 years). Presenting VA was 1.1 ± 0.8 logarithm of the minimum angle of resolution (LogMAR) (Snellen ∼20/250). The median time from presentation to RD surgery was 1.7 months (IQR, 0.8-4.1 months), and the mean preoperative VA was 1.6 ± 0.8 LogMAR (Snellen ∼20/800). Small-gauge pars plana vitrectomy (PPV) with or without a scleral buckle (SB) was performed for all eyes with an overall single-surgery success rate of 63.6%, with no statistically significant differences in visual/anatomic outcomes between PPV and PPV/SB cases. Silicone oil was used for tamponade in 33 (97.1%) cases and was removed in 10 (30.3%) with good anatomic and final functional outcomes (Snellen âˆ¼20/80). Independent predictors of recurrent RD included the female sex (hazard ratio, 8.38; 95% confidence interval, 2.03-34.68; P < 0.01) and zone 1 retinitis involvement at presentation (hazard ratio, 10.95; 95% confidence interval, 2.12-56.48; P < 0.01). The mean VA at 1 year (VA1year) and at the final follow-up both had a Snellen equivalent of 20/640 (P > 0.05 for both compared with preoperative VA, respectively). Eyes that achieved single-surgery success had VA1year of 20/200 versus hand movements in those with single-surgery failure (P < 0.01). On multivariate linear regression, younger age (P = 0.04) and better presenting VA (P < 0.01) were both associated with better VA1year. CONCLUSIONS: Moderate single-surgery anatomic success can be achieved with modern vitreoretinal surgical techniques for ARN-related RD, although visual outcomes remain poor. Further studies investigating interventions for increasing single-surgery success rates, for the inflammatory complications of ARN, and for preventing ARN-related RD are needed.

Biomolecular Modeling and Simulation: A Prospering Multidisciplinary Field.

We reassess progress in the field of biomolecular modeling and simulation, following up on our perspective published in 2011. By reviewing metrics for the field's productivity and providing examples of success, we underscore the productive phase of the field, whose short-term expectations were overestimated and long-term effects underestimated. Such successes include prediction of structures and mechanisms; generation of new insights into biomolecular activity; and thriving collaborations between modeling and experimentation, including experiments driven by modeling. We also discuss the impact of field exercises and web games on the field's progress. Overall, we note tremendous success by the biomolecular modeling community in utilization of computer power; improvement in force fields; and development and application of new algorithms, notably machine learning and artificial intelligence. The combined advances are enhancing the accuracy andscope of modeling and simulation, establishing an exemplary discipline where experiment and theory or simulations are full partners.

Pachychoroid spectrum disease.

Recent improvements in ophthalmic imaging have led to the identification of a thickened choroid or pachychoroid to be associated with a number of retinal diseases. The number of conditions linked to this phenotype has continued to widen with specific endophenotypes found within the pachychoroid spectrum. The spectrum includes choroidal features such as focal or diffuse choroidal thickening and thinning of the overlying inner choroid, and choroidal hyperpermeability as demonstrated by indocyanine green angiography. In addition, these diseases are associated with overlying retinal pigmentary changes and retinal pigment epithelial dysfunction and may also be associated with choroidal neovascularization. This article provides a comprehensive review of the literature looking at diseases currently described within the pachychoroid spectrum including central serous chorioretinopathy, pachychoroid pigment epitheliopathy, pachychoroid neovasculopathy, polypoidal choroidal vasculopathy/aneurysmal type 1 neovascularization, peripapillary pachychoroid disease and focal choroidal excavation. We particularly focus on clinical imaging, genetics and pathological findings in these conditions with the aim of updating evidence suggesting a common aetiology between diseases within the pachychoroid spectrum.

Outcomes of pars plana vitrectomy with subretinal tissue plasminogen activator injection and pneumatic displacement of fovea-involving submacular haemorrhage.

OBJECTIVE: Fovea-involving subretinal haemorrhage is challenging to manage with uncertain visual outcomes. We reviewed outcomes of patients with fovea-involving macular haemorrhage treated with pars plana vitrectomy (PPV) and subretinal tissue plasminogen activator (tPA) with pneumatic displacement. METHODS AND ANALYSIS: This is a retrospective interventional case series. All patients with submacular haemorrhage who underwent PPV with subretinal tPA injection were included. Reasons for exclusion encompassed patients who underwent intravitreal tPA injection in the office without surgery, insufficient follow-up or documentation. Primary outcomes of interest were postoperative visual acuity (VA) at month 1 and 3. Secondary outcomes were median VA at month 3 by location of haemorrhage and underlying diagnosis. RESULTS: Thirty-seven total patients were included. The mean age was 68.2 years, with 54.1% (20/37) females. The most common aetiology was exudative macular degeneration (43.2%), followed by undifferentiated choroidal neovascularisation (CNV) (18.9%), polypoidal choroidal vasculopathy (18.9%), traumatic CNV (10.8%), macroaneurysm (5.4%) and proliferative diabetic retinopathy (2.7%). Median preoperative VA was 20/2000, postoperative month 1 was 20/347 (p<0.01), improving to 20/152 (p<0.01) at month 3. Proportion of patients gaining vision 3+ lines in vision was 15/36 (42%). Mean preoperative central subfield thickness on optical coherence tomography was 512.2 µm for sub-retinal pigment epithelium haemorrhage and 648.2 µm for subretinal haemorrhage (p=0.48). Difference in VA by diagnosis was not significant (p=0.60). CONCLUSIONS: PPV with subretinal tPA injection and pneumatic displacement of submacular haemorrhage offers modest visual recovery for a diverse group of patients. Location of haemorrhage or specific diagnosis may not predict outcome.

ASSOCIATION OF RETINAL VEIN OCCLUSION WITH CARDIOVASCULAR EVENTS AND MORTALITY: A Systematic Review and Meta-analysis.

PURPOSE: Previous studies examining the association of retinal vein occlusion (RVO) and cardiovascular events have been inconsistent and have mostly focused on stroke and myocardial infarction. The goal of this study is to use meta-analysis to examine the available evidence examining the association of RVO with incident cardiovascular events and mortality. METHODS: Systematic review and meta-analysis of all longitudinal cohort studies published in PubMed, Embase, and the Cochrane Library from inception to April 7, 2018, that evaluated the association of baseline RVO and incident cardiovascular events and/or mortality, that provided multivariate-adjusted risk estimates with 95% confidence intervals (95% CIs), and that had average follow-up ≥1 year. The Newcastle-Ottawa scale was used to assess study quality. Multivariate-adjusted risk estimates with 95% CI along with study characteristics were extracted from each study, and pooled risk ratios (RRs) with 95% CI were generated using a random-effects model with inverse-variance weighting to account for heterogeneity. Main outcomes were incident stroke (fatal or nonfatal), myocardial infarction, heart failure, peripheral arterial disease, all-cause mortality, and cardiovascular mortality. RESULTS: Fifteen cohort studies with a total of 474,466 patients (60,069 with RVO and 414,397 without RVO) were included. Each study had Newcastle-Ottawa scale score ≥6, indicating moderate-to-high quality. Retinal vein occlusion was associated with increased risk of stroke (RR = 1.45; 95% CI, 1.31-1.60), myocardial infarction (RR = 1.26; 95% CI, 1.17-1.37), heart failure (RR = 1.53; 95% CI, 1.22-1.92), peripheral arterial disease (RR = 1.26; 95% CI, 1.09-1.46), and all-cause mortality (RR = 1.36; 95% CI, 1.02-1.81), but was not associated with increased risk of cardiovascular mortality (RR = 1.78; 95% CI, 0.70-4.48). CONCLUSION: This review suggests patients with RVO have an increased risk of cardiovascular events and all-cause mortality. More studies are needed to determine the highest risk periods for cardiovascular events and mortality after RVO and whether immediate cardiovascular evaluation and intervention will improve outcomes.

Upper limit for angular compounding speckle reduction.

Angular compounding is a technique for reducing speckle noise in optical coherence tomography that is claimed to significantly improve the signal-to-noise ratio (SNR) of images without impairing their spatial resolution. Here, we examine how focal point movements caused by optical aberrations in an angular compounding system may produce unintended spatial averaging and concomitant loss of spatial resolution. Experimentally, we accounted for such aberrations by aligning our system and measuring distortions in images and found that when the distortions were corrected, the speckle reduction by angular compounding was limited. Our theoretical analysis using Monte Carlo simulations indicates that "pure" angular compounding (i.e., with no spatial averaging) over our full numerical aperture (13° in air) can improve the SNR by not more than a factor of 1.3. Illuminating only a partial aperture cannot improve this factor compared to a spatial averaging system with equivalent loss of resolution. We conclude that speckle reduction using angular compounding is equivalent to spatial averaging. Nonetheless, angular compounding may be useful for improving images in applications where the depth of field is important. The distortions tend to be the greatest off the focal plane, and so angular compounding combined with our correction technique can reduce speckle with a minimal loss of resolution across a large depth of field.

ASSOCIATION OF OBSTRUCTIVE SLEEP APNEA WITH CENTRAL SEROUS CHORIORETINOPATHY AND CHOROIDAL THICKNESS: A Systematic Review and Meta-Analysis.

PURPOSE: Obstructive sleep apnea (OSA) has been associated with an array of ocular disorders. This systematic review aims to investigate the association of OSA with central serous chorioretinopathy (CSCR) and subfoveal choroidal thickness changes on enhanced depth imaging optical coherence tomography. METHODS: Systematic review and meta-analysis of all articles published up to November 2017 examining rate of OSA in patients with CSCR versus controls or examining subfoveal choroidal thickness measurements on enhanced depth imaging optical coherence tomography in patients with OSA versus controls. Pooled odds ratios and weighted mean difference with 95% confidence intervals (CIs) were calculated. RESULTS: For the CSCR/OSA analysis, 7,238 patients (1,479 with CSCR and 5,759 controls) from 6 studies were eligible. For the choroidal thickness/OSA analysis, 778 eyes of 778 patients (514 with OSA and 264 controls) from 9 studies were eligible. Patients with CSCR had a 1.56 increased odds of having OSA than controls (odds ratio, 1.56; 95% CI, 1.16-2.10). There was no statistically significant difference in choroidal thickness between mild OSA subjects and controls (weighted mean difference = -3.17; 95% CI, -19.10 to 12.76). Patients with moderate OSA (weighted mean difference = -24.14; 95% CI, -42.16 to -6.12) and severe OSA (weighted mean difference = -51.19; 95% CI, -99.30 to -3.08) had thinner choroidal thickness measurements than controls. CONCLUSION: In summary, our results suggest that patients with CSCR are more likely to have OSA, and that moderate/severe OSA is associated with smaller subfoveal choroidal measurements on enhanced depth imaging optical coherence tomography.

Acute Solar Retinopathy Imaged With Adaptive Optics, Optical Coherence Tomography Angiography, and En Face Optical Coherence Tomography.

IMPORTANCE: Solar retinopathy is a rare form of retinal injury that occurs after direct sungazing. OBJECTIVE: To enhance understanding of the structural changes that occur in solar retinopathy by obtaining high-resolution in vivo en face images. DESIGN, SETTING, AND PARTICIPANT: Case report of a young adult woman who presented to the New York Eye and Ear Infirmary with symptoms of acute solar retinopathy after viewing the solar eclipse on August 21, 2017. MAIN OUTCOMES AND MEASURES: Results of comprehensive ophthalmic examination and images obtained by fundus photography, microperimetry, spectral-domain optical coherence tomography (OCT), adaptive optics scanning light ophthalmoscopy, OCT angiography, and en face OCT. RESULTS: The patient was examined after viewing the solar eclipse. Visual acuity was 20/20 OD and 20/25 OS. The patient was left-eye dominant. Spectral-domain OCT images were consistent with mild and severe acute solar retinopathy in the right and left eye, respectively. Microperimetry was normal in the right eye but showed paracentral decreased retinal sensitivity in the left eye with a central absolute scotoma. Adaptive optics images of the right eye showed a small region of nonwaveguiding photoreceptors, while images of the left eye showed a large area of abnormal and nonwaveguiding photoreceptors. Optical coherence tomography angiography images were normal in both eyes. En face OCT images of the right eye showed a small circular hyperreflective area, with central hyporeflectivity in the outer retina of the right eye. The left eye showed a hyperreflective lesion that intensified in area from inner to middle retina and became mostly hyporeflective in the outer retina. The shape of the lesion on adaptive optics and en face OCT images of the left eye corresponded to the shape of the scotoma drawn by the patient on Amsler grid. CONCLUSIONS AND RELEVANCE: Acute solar retinopathy can present with foveal cone photoreceptor mosaic disturbances on adaptive optics scanning light ophthalmoscopy imaging. Corresponding reflectivity changes can be seen on en face OCT, especially in the middle and outer retina. Young adults may be especially vulnerable and need to be better informed of the risks of viewing the sun with inadequate protective eyewear.

Geriatric patients are predisposed to strabismus following thyroid-related orbital decompression surgery: A multivariate analysis.

Geriatric patients (age ≥ 65) are prone to complications after surgery and are at risk for severe thyroid eye disease (TED). In this study, we aim to identify preoperative demographic and TED patterns associated with geriatric patients who underwent decompression surgery, to examine the effect of age on postoperative strabismus rates, and to identify factors that may contribute to postoperative strabismus in the geriatric subgroup. We retrospectively reviewed patients who underwent thyroid-related orbital decompression surgery at the Kellogg Eye Center, University of Michigan, between 1999 and 2014. Primary outcome was postoperative strabismus requiring palliation with prisms and/or strabismus surgery. Descriptive, univariate, and multivariable logistic regression analyses were used to define association of geriatric age with postoperative strabismus and determine predictors of postoperative strabismus. Of 241 patients, 41 (17.0%) were geriatric. They were less likely to undergo bilateral decompression (P = 0.012), less likely to be current smokers at time of decompression (P = 0.002), and more likely to have preoperative primary gaze diplopia (P = 0.001). Postoperative strabismus rates for geriatric patients (≥ 65 years of age), ages 50-65, 30-50, and < 30, were 73.2%, 41.3%, 31.9%, and 15.8%, respectively (P = 0.002). On multivariable analysis, geriatric age remained an independent risk factor for postoperative strabismus when compared to each age group (P ≤ 0.001). Among geriatric patients in subgroup multivariable analysis, balanced as opposed to lateral wall decompression (P = 0.038) and shorter TED duration (P = 0.031) were independently predictive of postoperative strabismus.