Shotgun lipidomics of human subretinal fluids under rod-dominant retina reveals cone-dominated lipids.

Subretinal fluid (SRF) accumulates between photoreceptor outer segments and retinal pigment epithelium during rhegmatogenous retinal detachment. Biomolecular components such as lipids originate from cells surrounding the SRF. Knowledge of the composition of these molecules in SRF potentially provides mechanistic insight into the physiologic transfer of lipids between retinal tissue compartments. Using mass spectrometry and tandem mass spectrometry analysis on an electrospray ionization quadrupole-time-of-flight mass spectrometer, we identified a total of 115 lipid molecular species of 11 subclasses and 9 classes in two samples from two patients with rhegmatogenous retinal detachment. These included 47 glycerophosphocholines, 6 glycerophosphoethanolamines, 1 glycerophosphoinositol, 18 sphingomyelins, 9 cholesteryl esters, free cholesterol, 3 ceramides, 22 triacylglycerols and 8 free fatty acids. Glycerophosphocholines were of the highest intensity. By minimizing the formation of different adduct forms or clustering ions of different adducts, we determined the relative intensity of lipid molecular species within the same subclasses. The profiles were compared with those of retinal cells available in the published literature. The glycerophosphocholine profile of SRF was similar to that of cone outer segments, suggesting that outer segment degradation products are constitutively released into the interphotoreceptor matrix, appearing in SRF during detachment. This hypothesis was supported by the retinal distributions of corresponding lipid synthases' mRNA expression obtained from an online resource based on publicly available single-cell sequencing data. In contrast, based on lipid profiles and relevant gene expression in this study, the sources of free cholesterol and cholesteryl esters in SRF appeared more ambiguous, possibly reflecting that outer retina takes up plasma lipoproteins. Further studies to identify and quantify lipids in SRF will help better understand etiology of diseases relevant to outer retina.

Quantitative Autofluorescence at AMD's Beginnings Highlights Retinal Topography and Grading System Differences: ALSTAR2 Baseline.

INTRODUCTION: The aims of the study were to describe baseline quantitative (short-wavelength) autofluorescence (qAF) findings in a large pseudophakic cohort at age-related macular degeneration (AMD)'s beginnings and to assess qAF8 as an outcome measure and evaluate Age-Related Eye Disease Study (AREDS) and Beckman grading systems. METHODS: In the ALSTAR2 baseline cohort (NCT04112667), 346 pseudophakic eyes of 188 persons (74.0 ± 5.5 years) were classified as normal (N = 160 by AREDS, 158 by Beckman), early AMD (eAMD) (N = 104, 66), and intermediate AMD (iAMD) (N = 82, 122). Groups were compared via mean qAF intensities in a 6°-8° annulus (qAF8) and maps of differences between observations and the overall mean, divided by standard deviation (Z-score). RESULTS: qAF8 did not differ significantly among diagnostic groups by either stratification (p = 0.0869 AREDS; p = 0.0569 by Beckman). Notably, 45 eyes considered eAMD by AREDS became iAMD by Beckman. For AREDS-stratified eyes, Z-score maps showed higher centrally located qAF for normal, near the mean in eAMD, and lower values for iAMD. Maps deviated from this pattern for Beckman-stratified eyes. CONCLUSIONS: In a large sample of pseudophakic eyes, qAF8 does not differ overall from normal aging to iAMD but also does not capture the earliest AMD activity in the macula lutea. AREDS classification gives results more consistent with a slow decline in histologic autofluorescence than Beckman classification.

Transthyretin proteoforms of intraocular origin in human subretinal fluid.

Understanding the molecular composition of ocular tissues and fluids could inform new approaches to prevalent causes of blindness. Subretinal fluid accumulating between the photoreceptor outer segments and retinal pigment epithelium (RPE) is potentially a rich source of proteins and lipids normally cycling among outer retinal cells and choroid. Herein, intact post-translationally modified proteins (proteoforms) were extracted from subretinal fluids of five patients with rhegmatogenous retinal detachment (RRD), analyzed by tandem mass spectrometry, and compared to published data on these same proteins as synthesized by other organs. Single-nuclei transcriptomic data from non-diseased human retina/RPE were used to identify whether proteins in subretinal fluid were of potential ocular origin. Two human donor eyes with normal maculas were immunoprobed for transthyretin (TTR) with appropriate controls. The three most abundant proteins detected in subretinal fluid were albumin, TTR, and apolipoprotein A-I. Remarkably, TTR relative to the other proteins was more abundant than its serum counterpart, suggestive of TTR being synthesized predominantly locally. Six proteoforms of TTR were detected, with the relative amount of glutathionylated TTR being much higher in the subretinal fluid (12-43%) than values reported for serum (<5%) and cerebrospinal fluid (0.4-13%). Moreover, a putative glycosylated TTR dimer of 32,428 Da was detected as the fourth most abundant protein. The high abundance of TTR and putative TTR dimer in subretinal fluid was supported by analysis of available single-nuclei transcriptomic data, which showed strong and specific signal for TTR in RPE. Immunohistochemistry further showed strong diffuse TTR immunoreactivity in choroidal stroma that contrasted with vertically aligned signal in the outer segment zone of the subretinal space and negligible signal in RPE cell bodies. These results suggest that TTR in the retina is synthesized intraocularly, and glutathionylation is crucial for its normal function. Further studies on the composition, function, and quantities of TTR and other proteoforms in subretinal fluid could inform mechanisms, diagnostic methods, and treatment strategies for age-related macular degeneration, familial amyloidosis, and other retinal diseases involving dysregulation of physiologic lipid transfer and oxidative stress.

Visual outcomes of macula-involving rhegmatogenous retinal detachment in patients with and without age-related macular degeneration.

BACKGROUND: The prognosis for patients with macula-off rhegmatogenous retinal detachment (RRD) and concomitant age-related macular degeneration (AMD) is not well known. The purpose of this study is to compare visual outcomes in macula-off RRD in eyes with AMD versus a group of comparison eyes without AMD. METHODS: This was a retrospective chart review of 1149 patients. A total of 191 eyes met study criteria, 162 non-AMD eyes (controls), and 29 AMD eyes. The main outcome measure was postoperative visual acuity following pars plana vitrectomy (PPV), scleral buckle (SB), or combined PPV/SB in control eyes versus AMD eyes. This was compared using Fisher's exact test. RESULTS: There was a statistically significant difference in postoperative visual acuity by AMD status, with those without AMD having a worse visual outcome overall (p = 0.0048). A similar percentage of AMD versus non-AMD eyes achieved vision better than 20/40. More patients in the non-AMD group achieved a final visual acuity between 20/40 and 20/200. Of patients with AMD, more had vision worse than 20/200 though 58% maintained functional vision (better than 20/200). Those without AMD had a higher frequency of Count Fingers (CF), Hand Motion (HM), Light Perception (LP), or No Light Perception (NLP) vision (p = 0.023). CONCLUSIONS: Though postoperative visual acuity was worse overall in the non-AMD group with a higher frequency of patients having final vision of CF, HM, LP, or NLP, this is likely a function of the difference in sample size and composition between the two groups. Importantly, this study suggests AMD patients can expect similar outcomes to non-AMD patients after RRD repair. We conclude that AMD patients can achieve functional vision after RRD surgery, similar to those without AMD.

Objective Vision-related Indications for Clear and Tinted Football Helmet Visors.

SIGNIFICANCE: Football helmet visors are popular among players and may increase safety. However, they may also be costly or impractical, or impair the evaluation of head and neck injury. Determining an objective list of vision-related clinical conditions may help meet risk-benefit ratios while increasing access to care to athletes with special needs. PURPOSE: The purpose of this study was to determine an objective list of vision-related conditions that may benefit from clear and tinted football helmet visor use in athletes. METHODS: After comprehensive dilated eye examinations on 58 Division I collegiate football players at the University of Alabama at Birmingham between February 2017 and June 2018, an expert panel in vision care, sports medicine, and football equipment convened to determine vision-related conditions most important for clear or tinted football helmet visor use. RESULTS: In August 2018, the list drafted by the expert vision and sports medical panel in which a clear football helmet visor might be justified included conditions associated with retinal detachment and unilateral or binocular vision loss as well as high refractive error, refractive surgery, corneal compromise, and other conditions, which would necessitate additional eye protection. Of the 58 players examined, 3 (5%) were determined to have eye conditions that would require a clear visor as deemed by the expert panel, and 3 (5%) were determined to have eye conditions for which a clear visor was recommended. No players met indications for a tinted visor including congenital eye conditions that limit useful vision in daylight or bright-light environments, acquired conditions that may increase light sensitivity, and light-induced systemic conditions. CONCLUSIONS: This objective list of eye and vision-related systemic conditions is intended to mitigate the risk of long-term eye damage and/or vision deprivation. Clear and especially tinted football helmet visors require the sports medicine team to evaluate factors that will maximize the vision, head, and neck health of the athlete while increasing accessibility to sports for individuals with unique abilities.

Functionally validated imaging endpoints in the Alabama study on early age-related macular degeneration 2 (ALSTAR2): design and methods.

BACKGROUND: Age-related macular degeneration (AMD), a leading cause of irreversible vision impairment in the United States and globally, is a disease of the photoreceptor support system involving the retinal pigment epithelium (RPE), Bruch's membrane, and the choriocapillaris in the setting of characteristic extracellular deposits between outer retinal cells and their blood supply. Research has clearly documented the selective vulnerability of rod photoreceptors and rod-mediated (scotopic) vision in early AMD, including delayed rod-mediated dark adaptation (RMDA) and impaired rod-mediated light and pattern sensitivity. The unifying hypothesis of the Alabama Study on Early Macular Degeneration (ALSTAR2) is that early AMD is a disease of micronutrient deficiency and vascular insufficiency, due to detectable structural changes in the retinoid re-supply route from the choriocapillaris to the photoreceptors. Functionally this is manifest as delayed rod-mediated dark adaptation and eventually as rod-mediated visual dysfunction in general. METHODS: A cohort of 480 older adults either in normal macular health or with early AMD will be enrolled and followed for 3 years to examine cross-sectional and longitudinal associations between structural and functional characteristics of AMD. Using spectral domain optical coherence tomography, the association between (1) subretinal drusenoid deposits and drusen, (2) RPE cell bodies, and (3) the choriocapillaris' vascular density and rod- and cone-mediated vision will be examined. An accurate map and timeline of structure-function relationships in aging and early AMD gained from ALSTAR2, especially the critical transition from aging to disease, will identify major characteristics relevant to future treatments and preventative measures. DISCUSSION: A major barrier to developing treatments and prevention strategies for early AMD is a limited understanding of the temporal interrelationships among structural and functional characteristics while transitioning from aging to early AMD. ALSTAR2 will enable the development of functionally valid, structural biomarkers for early AMD, suitable for use in forthcoming clinical trials as endpoint/outcome measures. The comprehensive dataset will also allow hypothesis-testing for mechanisms that underlie the transition from aging to AMD, one of which is a newly developed Center-Surround model of cone resilience and rod vulnerability. TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT04112667, October 7, 2019.

Vitrectomy and Vitrector Port Needle Biopsy of Choroidal Melanoma for Gene Expression Profile Testing Immediately before Brachytherapy.

PURPOSE: Transvitreal and transscleral needle biopsy can result in complications including vitreous hemorrhage and retinal detachment. This study evaluated a technique using 25-gauge vitrectomy as an adjunct to needle biopsy immediately before brachytherapy to minimize these complications and preserve good visual acuity. DESIGN: Retrospective, observational case series. PARTICIPANTS: Fifty-seven consecutive eyes of 57 patients with treatment-naïve medium choroidal melanomas without extraocular extension from July 2012 through September 2015. METHODS: Fifty-seven consecutive eyes of 57 patients with a clinically diagnosed choroidal melanoma underwent complete 25-gauge posterior vitrectomy followed by transvitrector port fine-needle aspiration biopsy of the tumor immediately before implantation of a radioactive iodine 125 plaque as treatment for the tumor. Cytopathologic analysis was not performed on the tumor aspirates in this study. MAIN OUTCOME MEASURES: Best-corrected postoperative visual acuity, postoperative complications of the reported technique, implantation tumor development, local tumor recurrence, presence of metastatic disease after surgery, and sufficiency of the tumor aspirates obtained by the reported technique for successful gene expression profile testing and prognostic classification. RESULTS: Mean preoperative and postoperative visual acuities were similar (20/60 vs. 20/80, respectively). Mean tumor thickness was 5.0 mm (range, 2.5-10 mm) and mean tumor basal diameter was 13.1 mm (range, 7-22 mm). Only 1 of 57 eyes (1.8%) showed a transient vitreous hemorrhage, biopsy yield was 100% for genetic analysis, and no patients showed recurrence or implantation tumor at the vitrector site. CONCLUSIONS: Combined 25-gauge posterior vitrectomy and 25-gauge trans-vitrector port needle aspiration biopsy immediately before brachytherapy is excellent for obtaining tumor aspirate for gene expression profiling while controlling for hemostasis, resulting in few complications.

PNEUMATIC VITREOLYSIS FOR RELIEF OF VITREOMACULAR TRACTION.

PURPOSE: To evaluate the outcome of perfluoropropane (C3F8) gas injection for symptomatic vitreomacular traction (VMT) with or without Stage 2 macular hole (MH). METHODS: A retrospective review of eyes with VMT treated with 0.3 mL of C3F8 gas was performed. Patients avoided the supine position until gas resolution. Patients with small MH maintained partial face-down positioning. RESULTS: Forty-nine consecutive patients (50 eyes) with symptomatic VMT underwent pneumatic vitreolysis between 2010 and 2016. A posterior vitreous detachment developed in 43 eyes (86.0%) after a single gas injection, at a median of 3.0 weeks. Twenty-eight of 35 eyes (80.0%) with VMT only and all 15 eyes (100%) with a small Stage 2 MH developed a posterior vitreous detachment, with MH closure in 10 of 15 eyes (66.7%). Median baseline and last best spectacle-corrected visual acuities were 20/50 and 20/40, respectively (P < 0.001). Mean follow-up time was 11.1 ± 9.9 months. Rate of posterior vitreous detachment was reduced with presence of diabetes mellitus (25%) and with thick cellophane membrane (50%). Univariate analysis showed increased VMT release for eyes with VMT extent within 1 disk area (χ = 13.1, P = 0.002), eyes with absence of diabetes mellitus (χ = 8.8, P = 0.007), and eyes with Stage 2 MH (χ = 5.47, P = 0.019); there was a trend between success and lack of thick cellophane membrane (χ = 3.32, P = 0.068). Results using logistic regression also showed younger age (P = 0.012), followed by better baseline best spectacle-corrected visual acuity (P = 0.044), lack of diabetes mellitus (P = 0.077), and female gender (P = 0.045) to be predictors of increased VMT release. One VMT-only eye formed a MH and another VMT-only eye developed a retinal detachment. Both eyes responded to vitrectomy. CONCLUSION: Pneumatic vitreolysis with limited face-down position is a viable option for treating VMT with few adverse events. More studies are needed to elucidate its indications, benefits, and risks.

Long-Term Outcomes of Vitrectomy for Idiopathic Epiretinal Membrane With Internal Limiting Membrane Removal in Patients With Good Preoperative Visual Acuity.

Purpose: To evaluate the long-term visual results of vitrectomy with epiretinal membrane (ERM) and internal limiting membrane (ILM) removal for idiopathic ERM in eyes with a preoperative visual acuity (VA) of 20/50 or better. Methods: This retrospective review of a consecutive case series comprised 337 patients. Of these, 36 eyes of 36 patients had ERM and ILM removal from 2017 to 2018. Inclusion criteria included a subjective decrease in VA, a preoperative VA of 20/50 or better, vitrectomy with ERM and ILM removal for ERM, and a minimum 6-month follow-up. Paired t tests were used to determine the statistical significance (P < .05) of VA changes postoperatively. Results: The mean (±SD) best-corrected logMAR VA improved to a maximum of 0.125 ± 0.09 (Snellen equivalent 20/26.4) at a mean of 11.1 months postoperatively (P < .001). The VA continued to significantly improve over the long term (mean, 41.6 months; range, 6-63; P < .001). Overall long-term data trended heavily toward VA improvement (25/36 patients [69.4%]) and stability (10/36 patients [27.7%)] after ERM and ILM removal, with only 1 patient (2.8%) having worse VA. There were no intraoperative or postoperative complications related to ERM and ILM removal. Conclusions: Surgery to remove idiopathic ERM and ILM for patients with significant symptoms and good preoperative VA may result in excellent long-term visual results.

Peripheral PRP in the Operating Room vs Standard Clinic PRP for the Initial Treatment of PDR.

Purpose: To compare the long-term outcomes of standard panretinal photocoagulation (PRP) performed in the operating room (OR) with peripheral PRP performed in the clinic in treatment-naïve patients with proliferative diabetic retinopathy (PDR). Methods: Consecutive cases from 2017 to 2022 were retrospectively reviewed. Exclusion criteria included previous PRP, pars plana vitrectomy performed at the time of the initial PRP, PRP performed in another setting within 3 months of the initial treatment, a documented plan for future PRP at the time of the initial treatment, and less than 3 years of follow-up. Negative binomial regressions were used to compare the number of subsequent interventions between the 2 groups and t tests to compare the visual acuity (VA) outcomes. Results: Of the 961 eyes of 679 patients screened, 82 eyes of 53 patients met the inclusion criteria. The initial PRP was performed in the OR (OR cohort) in 57 eyes of 38 patients and in the clinic (clinic cohort) in 25 eyes of 15 patients. The OR cohort had a mean of 0.4 subsequent surgeries and 0.8 subsequent PRP treatments and the clinic cohort, 0.8 subsequent surgeries (P < .05) and 1.8 subsequent PRP treatments (P < .05). No significant between-group difference was found in the VA outcomes over the long-term follow-up (mean, 44.2 months). Conclusions: Peripheral PRP performed in the OR resulted in fewer subsequent interventions than standard PRP in the clinic and may afford better control of PDR.

Scleral Fixated Secondary IOLs: An Outcomes Comparison Between the Yamane and Gore-Tex-Sutured Techniques.

BACKGROUND AND OBJECTIVE: Among secondary intraocular lens (IOL) techniques, scleral fixated IOLs (SFIOLs) offer advantages in cases without capsular support. In this article, we compare outcomes between two types of Gore-Tex scleral sutured IOLs with the Yamane technique. PATIENTS AND METHODS: This study was a retrospective chart review of patients who underwent SFIOL implantation. RESULTS: Analysis revealed a statistically significant improvement in final postoperative visual acuity (VA) for sutured SFIOLs (P < 0.001, Envista (n = 29) 95% CI 0.47 to 1.04, Akreos (n = 23) 95% CI 0.32 to 0.81) with no statistical improvement in the Yamane group (P = 0.44, n = 15, 95% CI -0.33 to 0.71). Outcomes analysis revealed greater incidences of cystoid macular edema (CME) in the Yamane cohort (P < 0.05) and a higher rate of reoperations in the Akreos cohort (P < 0.02). All complications related to suture material (n = 4) and IOL decentration (n = 2) occurred in the sutured SFIOL group. CONCLUSIONS: The sutureless Yamane technique offered fewer subsequent surgeries and suture-specific complications while revealing diminished VA improvement in long-term follow-up compared to the sutured SFIOLs. [Ophthalmic Surg Lasers Imaging Retina 2024;55:384-390.].

Acute posterior multifocal placoid pigment epitheliopathy following COVID-19 infection.

Purpose: To report a case of acute posterior multifocal placoid pigment epitheliopathy (APMPPE) following COVID-19 infection. Observations: A 17-year-old female developed central scotomas and photopsias two weeks after SARS-CoV-2 diagnosis with polymerase chain reaction studies. She presented with poor visual acuity of 3/60 on the Feinbloom eye chart in the left eye. Dilated examination and multi-modal retinal imaging were consistent with the diagnosis of APMPPE, with noteworthy subretinal fluid. The patient was treated with an oral prednisone taper starting at 60mg with rapid resolution in subretinal fluid and improvement of visual acuity. Five weeks after presentation, visual acuity improved to 20/20 OU with complete resolution of the creamy white choroidal lesions and subretinal fluid. Conclusion: There is a growing body of literature reporting the ocular manifestations of COVID-19. Rarely inflammation of the retina or choroid have been associated with the infection. To the best of our knowledge, there are no prior reports that describe the clinical course or visual outcome in a patient with APMPEE associated with recent COVID-19 infection. Accordingly, we are not aware of any other reports that describe the treatment of APMPEE associated with COVID-19 with corticosteroids. The mechanism linking COVID-19 infection to inflammatory ocular disorders in unclear and likely multi-factorial.

Pembrolizumab-Induced Nodular Posterior Scleritis.

Purpose: To report a case of painless posterior scleritis presenting as a choroidal nodule in a patient with history of a tumor being treated with pembrolizumab. Methods: A case and its findings were analyzed, and a relevant literature review was performed. Results: A 20-year-old woman with a history of ependymoma presented with painless blurred vision in the right eye after being started on pembrolizumab for a tumor recurrence. Fundoscopy showed a solitary amelanotic choroidal lesion with surrounding subretinal fluid in the affected eye. Ultrasonography showed moderate internal reflectivity and fluid in Tenon capsule consistent with nodular posterior scleritis. After a course of systemic steroids and discontinuation of the pembrolizumab, the choroidal lesion completely resolved. Conclusions: Clinicians should be aware of posterior scleritis as an ocular complication of this class of medications.

Macular and Plasma Xanthophylls Are Higher in Age-related Macular Degeneration than in Normal Aging: Alabama Study on Early Age-related Macular Degeneration 2 Baseline.

Purpose: Quantification of retinal xanthophyll carotenoids in eyes with and without age-related macular degeneration (AMD) via macular pigment optical volume (MPOV), a metric for xanthophyll abundance from dual wavelength autofluorescence, plus correlations to plasma levels, could clarify the role of lutein (L) and zeaxanthin (Z) in health, AMD progression, and supplementation strategies. Design: Cross-sectional observational study (NCT04112667). Participants: Adults ≥ 60 years from a comprehensive ophthalmology clinic, with healthy maculas or maculas meeting fundus criteria for early or intermediate AMD. Methods: Macular health and supplement use was assessed by the Age-related Eye Disease Study (AREDS) 9-step scale and self-report, respectively. Macular pigment optical volume was measured from dual wavelength autofluorescence emissions (Spectralis, Heidelberg Engineering). Non-fasting blood draws were assayed for L and Z using high-performance liquid chromatography. Associations among plasma xanthophylls and MPOV were assessed adjusting for age. Main Outcome Measures: Age-related macular degeneration presence and severity, MPOV in fovea-centered regions of radius 2.0° and 9.0°; plasma L and Z (µM/ml). Results: Of 809 eyes from 434 persons (89% aged 60-79, 61% female), 53.3% eyes were normal, 28.2% early AMD, and 18.5% intermediate AMD. Macular pigment optical volume 2° and 9° were similar in phakic and pseudophakic eyes, which were combined for analysis. Macular pigment optical volume 2° and 9° and plasma L and Z were higher in early AMD than normal and higher still in intermediate AMD (P < 0.0001). For all participants, higher plasma L was correlated with higher MPOV 2° (Spearman correlation coefficient [Rs] = 0.49; P < 0.0001). These correlations were significant (P < 0.0001) but lower in normal (Rs = 0.37) than early and intermediate AMD (Rs = 0.52 and 0.51, respectively). Results were similar for MPOV 9°. Plasma Z, MPOV 2°, and MPOV 9° followed this same pattern of associations. Associations were not affected by supplement use or smoking status. Conclusions: A moderate positive correlation of MPOV with plasma L and Z comports with regulated xanthophyll bioavailability and a hypothesized role for xanthophyll transfer in soft drusen biology. An assumption that xanthophylls are low in AMD retina underlies supplementation strategies to reduce progression risk, which our data do not support. Whether higher xanthophyll levels in AMD are due to supplement use cannot be determined in this study.

How Vision Is Impaired From Aging to Early and Intermediate Age-Related Macular Degeneration: Insights From ALSTAR2 Baseline.

Purpose: We hypothesize the first visual dysfunction in transitioning to early and intermediate age-related macular degeneration (AMD) is delayed rod-mediated dark adaptation (RMDA), owing to impaired photoreceptor sustenance from the circulation. This analysis from the Alabama Study on Early Age-related Macular Degeneration 2 provides insight on our framework's validity, comparing RMDA and other visual tests among older normal, early, and intermediate AMD eyes. Methods: AMD disease severity was determined via fundus photos using the Age-Related Eye Disease Study nine-step system. Visual functions evaluated were RMDA 5°, acuity, contrast sensitivity (photopic, mesopic), and light sensitivity for a macular grid (scotopic, mesopic, photopic). Presence versus absence of subretinal drusenoid deposits (SDD) was identified through multimodal imaging. Results: One eye from each of 481 persons (mean age, 72 years) was evaluated. All visual functions were significantly worse with increasing AMD disease severity. Using z-scores to standardize visual function measures across groups, the greatest difference in probability density functions between older normal and intermediate AMD was for RMDA. Early and intermediate AMD eyes with SDD present had longer rod intercept times than eyes with SDD absent. SDD absent eyes also exhibited delayed RMDA and wide probability density functions relative to normal eyes. Conclusions: Among the visual functions evaluated, RMDA best discriminates among normal, early AMD, and intermediate AMD eyes. The Alabama Study on Early Age-related Macular Degeneration 2 will evaluate whether AMD's natural history confirms our hypothesis at the 3-year follow-up. Translational Relevance: Results support a sequence of visual function impairments in aging and AMD, suggesting RMDA as a promising outcome for evaluating interventions in early disease.

Real-World Outcomes in Patients with Branch Retinal Vein Occlusion- (BRVO-) Related Macular Edema Treated with Anti-VEGF Injections Alone versus Anti-VEGF Injections Combined with Focal Laser.

The purpose of this study was to assess outcomes in a real-world nonclinical trial setting of antivascular endothelial growth factor (VEGF) injections alone vs. focal laser combined with anti-VEGF injections in patients with branch retinal vein occlusion- (BRVO-) related macular edema (ME). This study included 88 BRVO with ME patients who were treated over three years at both a tertiary referral center in the Birmingham metropolitan area and satellites in rural Alabama. One group received only anti-VEGF injections (n = 56); the other group received both anti-VEGF injections and focal laser (n = 32). The following outcome measures were evaluated: initial and final visual acuities (VA), initial central subfield thickness (CST) on OCT, number of injections, number of lasers, percentage of patients with a gain of 3 lines of VA, percentage of patients with VA better than or equal to 20/40, and percentage of patients with VA worse than or equal to 20/200. We found that there was no difference in initial VA (p=0.913) or CST (p=0.961) between the two groups. The injection only group required a median of 7 injections, while the combination group required a median of 4 injections, but this was not a statistically significant difference (p=0.117). There was no difference in final VA (p=0.414) or any of the other visual outcomes between the two groups. In conclusion, focal laser did not decrease the number of injections required or improve the VA in BRVO-related ME. Although visual outcomes were similar in both groups, focal laser does not appear to be of additional benefit in BRVO-related ME in the anti-VEGF era.

Branch retinal artery occlusion secondary to Bartonella henselae infection in a 13 year-old.

PURPOSE: To summarize the case of a 13 year-old boy diagnosed with a BRAO secondary to B. henselae infection. OBSERVATIONS: The patient presented with a sudden, unilateral, and painless scotoma. Fundoscopic findings and multimodal imaging were consistent with a BRAO with associated areas of intraretinal whitening along the involved artery. Upon further questioning, the patient reported having 15 cats at home. Antibodies were positive for B. henselae. The patient was treated with oral doxycycline 100 mg twice daily for 2 months with complete resolution of the retinal findings and the scotoma. CONCLUSIONS AND IMPORTANCE: B. henselae should be considered as a potential cause of retinitis and BRAO, even in pediatric-aged patients.

Local Abundance of Macular Xanthophyll Pigment Is Associated with Rod- and Cone-Mediated Vision in Aging and Age-Related Macular Degeneration.

Purpose: We assessed the association between the abundance of macular xanthophyll carotenoid pigment using dual-wavelength autofluorescence and multimodal vision testing including rod-mediated dark adaptation (RMDA), a measure of retinoid re-supply, in adults ≥60 years old with and without age-related macular degeneration (AMD). Methods: AMD severity was determined using the nine-step Age-Related Eye Disease Study grading. Tests probed cones (best-corrected visual acuity, contrast sensitivity), cones and rods (low-luminance visual acuity, low-luminance deficit, mesopic light sensitivity), or rods only (scotopic light sensitivity, RMDA). Signal attenuation by macular pigment optical density (MPOD) was estimated using a ratio of blue and green autofluorescence signal to yield mean MPOD in a 1°-diameter fovea-centered disk, mean MPOD in a 2°-diameter disk centered on a perifoveal RMDA test location, and macular pigment optical volume (MPOV, or integrated MPOD) in a 4°-diameter fovea-centered disk. Age-adjusted associations between vision and imaging measures were determined. Results: In 88 eyes of 88 subjects (age, 74.9 ± 5.8 years) with normal eyes (n = 32), early AMD (n = 23), or intermediate AMD (n = 33), foveal and perifoveal MPOD and MPOV were higher in the AMD eyes than in the normal eyes. At the RMDA test location, higher MPOD was unrelated to AMD severity but was associated with faster RMDA. Conclusions: In older adults with and without AMD, higher macular xanthophyll concentrations are associated with better best-corrected visual acuity and RMDA. Data are consistent with a model of cone resilience and rod vulnerability in aging and AMD and can be further explored in a larger sample study.

Toxoplasmosis chorioretinitis mimicking acute retinal necrosis associated with local corticosteroid.

BACKGROUND: The cases discussed highlight the atypical presentation and diagnostic dilemmas of toxoplasmosis with fulminant retinal necrosis and the potentially devastating visual outcomes of toxoplasma chorioretinitis following local corticosteroid exposure. CASE PRESENTATION: We report a series of three patients who presented with toxoplasmosis mimicking severe acute retinal necrosis. Patients were between 59 and 77 years old and had been exposed to local corticosteroids preceding our evaluation. All patients demonstrated diffuse retinal whitening with severe vision loss on presentation. Polymerase chain reaction testing (PCR) was diagnostic in two patients, and histopathologic examination of a vitrectomy specimen was diagnostic in one patient. All cases of retinitis resolved with anti-parasitic medication; however, visual acuity failed to improve in all patients due to disease severity and presentation. CONCLUSIONS: Local corticosteroid injection may trigger or exacerbate toxoplasmosis chorioretinitis, leading to fulminant retinal necrosis and severe vision loss. Toxoplasma chorioretinitis should be considered in the differential diagnosis of patients presenting with clinical features of acute retinal necrosis, particularly following local corticosteroid injection regardless of their baseline systemic immune status. Diagnostic vitrectomy may be helpful in patients in whom PCR testing is negative and ocular toxoplasmosis is suspected.

Hyperreflective Foci and Specks Are Associated with Delayed Rod-Mediated Dark Adaptation in Nonneovascular Age-Related Macular Degeneration.

PURPOSE: Hyperreflective foci (HRF) are OCT biomarkers for the progression of nonneovascular age-related macular degeneration (AMD) attributed to anteriorly migrated retinal pigment epithelial cells. We examined associations between rod- and cone-mediated vision and HRF plus smaller hyperreflective specks (HRS); we identified a histologic candidate for HRS. DESIGN: Cross-sectional study and histologic survey. PARTICIPANTS: Patients with healthy maculae (n = 34), early AMD (n = 26), and intermediate AMD (n = 41). METHODS: AMD severity was determined by color fundus photography. In OCT scans, HRF and HRS were counted manually. Vision tests probed cones (best-corrected visual acuity [VA], contrast sensitivity), mixed cones and rods (low-luminance VA, low-luminance deficit, mesopic light sensitivity), or rods (scotopic light sensitivity, rod-mediated dark adaptation [RMDA]). An online AMD histopathologic resource was reviewed. MAIN OUTCOME MEASURES: Vision in eyes assessed for HRF and HRS; histologic candidate for HRS. RESULTS: In 101 eyes of 101 patients, HRF and HRS were identified in 25 and 95 eyes, respectively, with good reliability. Hyperreflective foci were present but sparse in healthy eyes, infrequent in early AMD eyes, and frequent but highly variable among intermediate AMD eyes (mean±standard deviation [SD] number per eye, 0.1 ± 0.2, 0.2 ± 0.5, and 1.9 ± 3.4 for healthy, early AMD, and intermediate AMD eyes, respectively). Hyperreflective specks outnumbered HRF in all groups (mean±SD, 4.5 ± 3.2, 6.3 ± 5.8, and 19.4 ± 22.4, respectively). Delayed RMDA was associated strongly with more HRF and HRS (P < 0.0001). Hyperreflective foci also were associated with worse low-luminance VA (P = 0.0117). Hyperreflective specks were associated with worse contrast sensitivity (P = 0.0278), low-luminance VA (P = 0.0010), low-luminance deficit (P = 0.0031), and mesopic (P = 0.0018) and scotopic (P < 0.0001) sensitivity. By histologic analysis, cone lipofuscin was found in outer retinal layers of 25% of healthy aged eyes. CONCLUSIONS: Hyperreflective foci and HRS are markers of cellular activity associated with visual dysfunction, especially delayed RMDA, an AMD risk indicator assessing efficiency of retinoid resupply. Hyperreflective specks may represent lipofuscin translocating inwardly within cones. HRF and HRS may serve as structural end points in clinical trials targeting AMD stages earlier than atrophy expansion. These results should be confirmed in a larger sample.