Antisense oligonucleotide therapy for proline-23-histidine autosomal dominant retinitis pigmentosa.

PURPOSE OF REVIEW: To discuss antisense oligonucleotide (ASON) therapy for autosomal dominant retinitis pigmentosa (adRP) caused by the proline-23-histidine (P23H) mutation in the rhodopsin gene. RECENT FINDINGS: Viral and nonviral therapies to treat adRP are currently under investigation. A promising therapeutic option is a nonviral approach using ASONs. This form of genetic therapy has demonstrated a dose-dependent and highly selective reduction of P23H mutant rhodopsin mRNA in animal models, and it is currently being investigated as a human phase 1/2 clinical trial. SUMMARY: There are promising new therapies to treat adRP. ASON has shown encouraging results in animal models and has undergone a phase 1 clinical trial. ASON does not use a viral vector, is delivered with standard intravitreal injection, and its effects are reversible.

A Density Functional Theory Study of Optical Rotation in Some Aziridine and Oxirane Derivatives.

We present time-dependent density functional theory (TDDFT) calculations of the electronic optical rotation (ORP) for seven oxirane and two aziridine derivatives in the gas phase and in solution and compare the results with the available experimental values. For seven of the studied molecules it is the first time that their optical rotation was studied theoretically and we have therefore investigated the influence of several settings in the TDDFT calculations on the results. This includes the choice of the one-electron basis set, the exchange-correlation functional or the particular polarizable continuum model (PCM). We can confirm that polarized quadruple zeta basis sets augmented with diffuse functions are necessary for converged results and find that the aug-pc-3 basis set is a viable alternative to the frequently employed aug-cc-pVQZ basis set. Based on our study, we cannot recommend the generalized gradient functional KT3 for calculations of the ORP in these compounds, whereas the hybrid functional PBE0 gives results quite similar to the long-range correct CAM-B3LYP functional. Finally, we observe large differences in the solvent effects predicted by the integral equation formalism of PCM and the SMD variant of PCM. For the majority of solute/solvent combinations in this study, we find that the SMD model in combination with the PBE0 functional and the aug-pc-3 basis set gives the best agreement with the experimental values.

Update on maculopathy secondary to pentosan polysulfate toxicity.

PURPOSE OF REVIEW: The aim of the present review is to provide a comprehensive summary of available knowledge regarding toxic maculopathy secondary to pentosan polysulfate sodium (PPS). RECENT FINDINGS: PPS toxicity was described in 2018, and additional studies characterize it as dysfunction of the retinal pigment epithelium centered on the posterior pole, which can progress despite drug cessation. Requisite exposure can be as little as 0.325 kg and 2.25 years but averages closer to 1-2 kg and 10-15 years. Multimodal imaging should include near-infrared reflectance, optical coherence tomography, and fundus autofluorescence. Cross-sectional studies demonstrate evidence correlating cumulative dosing and the likelihood/severity of maculopathy. Early estimates of prevalence range from 12.7 to 41.7% depending on dosing, with overall rates around 20%. SUMMARY: Reasonable evidence associates maculopathy with extended exposure to PPS, with an average reported incidence of around 20% in patients with long-term exposures. Patients with unexplained retinal pigment epithelium changes and difficulty with dark adaptation should be questioned regarding PPS exposure, and patients with known exposure to PPS should be examined. Further research is needed to refine screening protocols. Currently, providers should consider baseline examination and examination at 5 years and/or 500 g of exposure followed by yearly screening.

Gene therapy beyond luxturna: a new horizon of the treatment for inherited retinal disease.

PURPOSE OF REVIEW: Gene therapy offers, for the first time, the possibility to cure diseases such as retinitis pigmentosa. The positive outcomes that led to the U.S. Food and Drug Administration (FDA) approval of Luxturna to treat Leber congenital amaurosis caused by RPE65 mutations created an optimistic atmosphere in the research, clinical and patient community. Despite this first success, we must understand that this is not a 'one treatment for all'. This review aims to explain the basic concepts of gene therapy and how they translate in different approaches that are utilized in ongoing clinical trials here reviewed. RECENT FINDINGS: In 2017, the FDA approved the first gene therapy treatment. In parallel, other approaches have gained attention. Different delivery methods (adeno-associated virus, lentivirus), injection sites (subretinal, intravitreal, suprachoroidal) and methodologies (gene replacement, silencing, editing) are currently being tested. SUMMARY: Gene therapy is an evolving field in medicine and ophthalmology. Its success and application depends on several factors that are specific to the disease to treat. For now, we know it's a relatively safe approach and we look forward to the continued advancements of current ongoing clinical trials.

Are serum autoantibodies associated with brain changes in systemic lupus erythematosus? MRI data from the Leiden NP-SLE cohort.

OBJECTIVE: The effect of serum autoantibodies on the brain of systemic lupus erythematosus (SLE) patients remains unclear. We investigated whether serum autoantibodies, individually and assessed in groups, are associated with specific brain-MRI abnormalities or whether these structural changes are associated with other SLE-related or traditional cardiovascular disease risk factors. METHODS: All patients underwent brain 3Tesla-MRI. White matter hyperintensities (WMHs), ischemic lesions, inflammatory-like lesions and cerebral atrophy were scored. Serum autoantibodies analyzed included lupus anticoagulant (LAC), anticardiolipine (aCL) IgG and IgM (first 3 also grouped into antiphospholipid autoantibodies (aPL)), anti-dsDNA, anti-SSA, anti-SSB, anti-RNP, and anti-Sm (the latter 5 grouped into SLE-related autoantibodies). Associations were assessed using logistic regression analysis adjusted for potential confounders. Furthermore, a sensitivity analysis including anti-Beta2 glycoprotein-1 antibodies (anti-ß2GP1) in the aPL group was performed and the potential modification role of the neuropsychiatric clinical status in the model was assessed. RESULTS: 325 patients (mean age 42 years (SD 14), 89% female) were included. The following MRI-brain abnormalities were found: WMHs (71%), lacunar infarcts (21%), gliosis (11%), micro-hemorrhages (5%), large hemorrhages (2%), inflammatory-like lesions (6%) and atrophy (14%). No associations were found between individual or total SLE-related autoantibodies and inflammatory-like lesions. A higher number of positive aPL was associated with lacunar infarcts (OR 1.37 (95%CI 1.02-1.99) and gliosis (OR 2.15 (1.37-3.37)). LAC was associated with lacunar infarcts in white matter (OR 3.38 (1.32-8.68)) and atrophy (OR 2.49 (1.01-6.15)), and aCL IgG with gliosis (OR 2.71 (1.05-7.02)). Among other variables, SLE patients with hypertension presented a higher chance for WMHs (OR 5.61 (2.52-12.48)) and lacunar infarcts in WM (OR 2.52 (1.10-5.74)) and basal ganglia (OR 8.34 (2.19-31.70)), while cumulative SLE-damage was correlated with lacunar infarcts in WM (OR 1.43 (1.07-1.90)), basal ganglia (OR 1.72 (1.18-2.51)) and cerebellum (OR 1.79 (1.33-2.41)). These associations were confirmed in the sensitivity analysis. CONCLUSIONS: Brain abnormalities in SLE represent different underlying pathogenic mechanisms. aPL are associated with ischemic brain changes in SLE, while the presence of SLE-related serum autoantibodies is not related to inflammatory-like lesions. Hypertension and cumulative SLE-damage associate with ischemic MRI-brain changes in SLE, suggesting the importance of accelerated atherosclerosis in this process.

Economic considerations and patients' preferences affect treatment selection for patients with rheumatoid arthritis: a discrete choice experiment among European rheumatologists.

OBJECTIVE: To compare the value that rheumatologists across Europe attach to patients' preferences and economic aspects when choosing treatments for patients with rheumatoid arthritis. METHODS: In a discrete choice experiment, European rheumatologists chose between two hypothetical drug treatments for a patient with moderate disease activity. Treatments differed in five attributes: efficacy (improvement and achieved state on disease activity), safety (probability of serious adverse events), patient's preference (level of agreement), medication costs and cost-effectiveness (incremental cost-effectiveness ratio (ICER)). A Bayesian efficient design defined 14 choice sets, and a random parameter logit model was used to estimate relative preferences for rheumatologists across countries. Cluster analyses and latent class models were applied to understand preference patterns across countries and among individual rheumatologists. RESULTS: Responses of 559 rheumatologists from 12 European countries were included in the analysis (49% females, mean age 48 years). In all countries, efficacy dominated treatment decisions followed by economic considerations and patients' preferences. Across countries, rheumatologists avoided selecting a treatment that patients disliked. Latent class models revealed four respondent profiles: one traded off all attributes except safety, and the remaining three classes disregarded ICER. Among individual rheumatologists, 57% disregarded ICER and these were more likely from Italy, Romania, Portugal or France, whereas 43% disregarded uncommon/rare side effects and were more likely from Belgium, Germany, Hungary, the Netherlands, Norway, Spain, Sweden or UK. CONCLUSIONS: Overall, European rheumatologists are willing to trade between treatment efficacy, patients' treatment preferences and economic considerations. However, the degree of trade-off differs between countries and among individuals.

European League Against Rheumatism (EULAR) recommendations for the management of psoriatic arthritis with pharmacological therapies: 2015 update.

BACKGROUND: Since the publication of the European League Against Rheumatism recommendations for the pharmacological treatment of psoriatic arthritis (PsA) in 2012, new evidence and new therapeutic agents have emerged. The objective was to update these recommendations. METHODS: A systematic literature review was performed regarding pharmacological treatment in PsA. Subsequently, recommendations were formulated based on the evidence and the expert opinion of the 34 Task Force members. Levels of evidence and strengths of recommendations were allocated. RESULTS: The updated recommendations comprise 5 overarching principles and 10 recommendations, covering pharmacological therapies for PsA from non-steroidal anti-inflammatory drugs (NSAIDs), to conventional synthetic (csDMARD) and biological (bDMARD) disease-modifying antirheumatic drugs, whatever their mode of action, taking articular and extra-articular manifestations of PsA into account, but focusing on musculoskeletal involvement. The overarching principles address the need for shared decision-making and treatment objectives. The recommendations address csDMARDs as an initial therapy after failure of NSAIDs and local therapy for active disease, followed, if necessary, by a bDMARD or a targeted synthetic DMARD (tsDMARD). The first bDMARD would usually be a tumour necrosis factor (TNF) inhibitor. bDMARDs targeting interleukin (IL)12/23 (ustekinumab) or IL-17 pathways (secukinumab) may be used in patients for whom TNF inhibitors are inappropriate and a tsDMARD such as a phosphodiesterase 4-inhibitor (apremilast) if bDMARDs are inappropriate. If the first bDMARD strategy fails, any other bDMARD or tsDMARD may be used. CONCLUSIONS: These recommendations provide stakeholders with an updated consensus on the pharmacological treatment of PsA and strategies to reach optimal outcomes in PsA, based on a combination of evidence and expert opinion.

Insulin, Hyperglycemia, and Severe Retinopathy of Prematurity in Extremely Low-Birth-Weight Infants.

OBJECTIVE: This study aims to determine the association between hyperglycemia, insulin therapy, and severe retinopathy of prematurity (ROP) in extremely low-birth-weight (ELBW) infants. STUDY DESIGN: In this retrospective database study, we included all ELBW infants who were ≤ 32 weeks gestational age (GA). We excluded infants without any ophthalmology evaluation and infants who died before 28 days of life. A multivariable model was constructed to determine the association between hyperglycemia, insulin use, and severe ROP. We defined hyperglycemia as blood glucose (BG) > 180 mg/dL. Covariates were GA, small for GA status, discharge year, sex, Apgar score at 5 minutes, mechanical ventilation, oxygen use, bacteremia, and postnatal steroid exposure. We defined severe ROP as ROP requiring bevacizumab, cryotherapy, laser therapy, or vitrectomy. Sensitivity analysis using BG > 150 mg/dL and > 200 mg/dL was performed. RESULTS: A total of 24,548 infants were included; 2,547 (10%) had severe ROP. Hyperglycemia alone was not associated with severe ROP (odds ratio [OR], 0.88; 95% confidence interval [CI], 0.66-1.17). Hyperglycemia and insulin use were not associated with severe ROP (OR, 1.43; 95% CI, 0.91-2.23). BG > 150 mg/dL and insulin use were associated with severe ROP (OR, 1.34; 95% CI, 1.02-1.76). CONCLUSIONS: Hyperglycemia alone was not associated with severe ROP in ELBW infants. However, we did observe a possible trend between the use of insulin and severe ROP.

Three-dimensional assessment of vascular and perivascular characteristics in subjects with retinopathy of prematurity.

PURPOSE: To study vascular features detected with spectral domain optical coherence tomography (SD-OCT) in subjects undergoing retinopathy of prematurity (ROP) screening. DESIGN: Cross-sectional study. PARTICIPANTS AND CONTROLS: Fifty-seven premature neonates, 10 with plus disease in at least 1 eye and 47 without plus disease. METHODS: Bedside noncontact SD-OCT imaging was performed after obtaining parental consent on 97 consecutive infants between January 2009 and September 2012. Fifty-seven subjects (31-49 weeks' post-menstrual age) who had an SD-OCT scan in at least 1 eye showing the edge of the optic nerve and at least 1 major retinal vascular arcade were included. One eye per subject was randomly selected for analysis. Two masked graders evaluated scans for (1) retinal vessel elevation, (2) scalloped retinal layers, (3) hyporeflective vessels, and (4) retinal spaces. To coalesce the weight of these features, a Vascular Abnormality Score by OCT (VASO) was created. For quantitative assessment of vessel elevation, retinal surface maps were created. MAIN OUTCOME MEASURES: Prevalence of SD-OCT vascular abnormalities, the VASO, intergrader agreement, and presence of elevation on surface maps. RESULTS: From among 67 SD-OCT characteristics that were recorded, the most common characteristics found were vessel elevation (44%), hyporeflective vessels (40%), scalloped layers (22%), and retinal spaces (11%). Features significantly associated with plus disease were vessel elevation (P = 0.01), hyporeflective vessels (P = 0.04), and scalloped retinal layers (P = 0.006). Intragrader agreement was between 74% and 90% for all features. The VASO was significantly higher in subjects with plus disease (P = 0.0013). On 3-dimensional SD-OCT volumes, eyes with plus disease had greater retinal surface elevation that more often matched en face retinal vascular patterns. CONCLUSIONS: We present a novel 3-dimensional analysis of vascular and perivascular abnormalities identified in SD-OCT images of eyes with ROP. The SD-OCT characteristics that are more common in eyes with plus disease provide the first in vivo demonstration of the effects of vascular dilation and tortuosity on perivascular tissue. The VASO and surface maps also delineate the severity of vascular pathology in plus disease. Further studies evaluating these findings in eyes with pre-plus versus normal posterior pole vessels may determine the usefulness of SD-OCT in the early detection of vascular abnormalities in ROP.

Evaluation of optic nerve development in preterm and term infants using handheld spectral-domain optical coherence tomography.

PURPOSE: To evaluate effects of prematurity on early optic nerve (ON) development and the usefulness of ON parameters as indicators of central nervous system (CNS) development and pathology. DESIGN: Prospective, cross-sectional, longitudinal study. PARTICIPANTS: Forty-four preterm infants undergoing retinopathy of prematurity (ROP) screening and 52 term infants. METHODS: We analyzed ON from portable handheld spectral-domain optical coherence tomography (SD-OCT) images (Bioptigen, Inc, Research Triangle Park, NC) of 44 preterm and 52 term infants. The highest-quality ON scan from either eye was selected for quantitative analysis. Longitudinal analysis was performed at 31-36 weeks and 37-42 weeks postmenstrual age (PMA). Preterm ON parameters also were assessed for correlation with indicators of cognitive, language, and motor development and CNS pathology. MAIN OUTCOME MEASURES: Vertical cup diameter (vCD), vertical disc diameter (vDD), vertical cup-to-disc ratio (vCDR), cup depth, and indicators of neurocognitive development and CNS pathology. RESULTS: At 37-42 weeks PMA, preterm infants had larger vCD and vCDR than term infants (908 vs. 700 µm [P<0.001] and 0.68 vs. 0.53 µm [P<0.001], respectively), whereas cup depth and vDD were not significantly different. Longitudinal changes (n = 26 preterm eyes; mean interval, 4.7 weeks) in vDD and in vCDR were an increase of 74 µm (P = 0.008) and decrease of 0.05 (P = 0.015), respectively. In preterm infants (n = 44), periventricular leukomalacia was associated with larger vCD (1084 vs. 828 µm; P = 0.005) and vCDR (0.85 vs. 0.63; P<0.001), posthemorrhagic hydrocephalus was associated with shallower cup (331 vs. 456 µm; P = 0.030), and clinical magnetic resonance imaging was associated with larger vCDR (0.73 vs. 0.64; P = 0.023). In 23 preterm infants with Bayley Scales of Infant Development scores, larger vCDR was associated with lower cognitive scores (P = 0.049). CONCLUSIONS: This is the first analysis of ON parameters in premature infants using SD-OCT. It demonstrated that by age of term birth, vCD and vCDR are larger in preterm infants who were screened for ROP than in term infants. In this prospective pilot study, ON parameters in these preterm infants associate weakly with CNS pathology and future cognitive development. Future prospective studies with larger numbers are necessary before further conclusions can be made.

A possible case of offspring sex manipulation as result of a biased adult sex ratio.

Although random meiosis should prevent the facultative adjustment of offspring sex ratio, theory predicts that females should produce more of the sex with the higher reproductive value. We reported a case of offspring sex ratio manipulation in grass wrens Cistothorus platensis. Males in better body condition would have higher reproductive value than females due to the potential for social polygyny and extra-pair fertilizations. On the other hand, local demography influences reproductive strategies in grass wrens as male abundance affects both social polygyny and extra-pair paternity frequencies. We evaluated whether females bias their brood sex ratio in response to adult sex ratio and nestling body condition (a proxy for female's prospects of producing high-quality males). Females raised more male offspring when males were less abundant in the population (female-biased adult sex ratio). However, we found no relationship between nestling body condition and brood sex ratio, suggesting that females did not bias the brood sex ratio towards males when able to raise nestlings in better body condition. Taken together, our results provide the first suggestive evidence that female birds can manipulate their offspring sex ratio in response to the adult sex ratio.

Novel missense WFS1 variant causing autosomal dominant atypical Wolfram syndrome.

BACKGROUND: In contrast to the classic autosomal recessive Wolfram syndrome, Wolfram-like syndrome (WLS) is an autosomal dominant disease caused by heterozygous variants in the WFS1 gene. Here, we present deep phenotyping of a mother and son with a WFS1 variant NM_006005.3:c.2508 G > T, p. (Lys836Asn) detected with next-generation sequencing, which is novel at the nucleotide level. In this Greek family, the proband and mother had sensorineural hearing loss and mild non-progressive vision loss with optic nerve atrophy. An initial optic atrophy panel that did not test for WFS1 was unremarkable, but a broader inherited retinal dystrophy panel found the WFS1 variant. CONCLUSION: This study highlights the importance of including WFS1 sequencing in the evaluation of optic nerve atrophy to discover syndromic conditions.

Anatomical and functional outcomes of bevacizumab treatment in pediatric autosomal recessive bestrophinopathy.

PURPOSE: To report functional and anatomical outcomes of anti-VEGF treatment in eyes with autosomal recessive Bestrophinopathy (ARB) presenting in the first decade of life. METHODS: Case series of four eyes from two siblings with compound heterozygous mutations in the BEST1 gene who were treated with eight monthly intravitreal bevacizumab (IVB) injections. Response to treatment was analyzed using fundus photography (CFP), fundus autofluorescence (FAF), optical coherence tomography (OCT), OCT angiography (OCTA), and Microperimetry (MP). RESULTS: Patient-1 (male, age 9 yrs.) with visual acuity of 20/20 OD and 20/50 OS. Patient-2 (female, age 10 yrs.), with visual acuity of 20/25 OD, 20/20 OS. All eyes had multifocal subretinal deposition of lipofuscin, subretinal fluid and three had choroidal neovascularization (CNV). Lipofuscin material reabsorbed in 2/4 eyes, the CNV regressed in 3/3, a bacillary detachment resolved (1/1) but the subretinal fluid did not change. Functional improvement in visual acuity was noted but MP showed scattered areas of reduced retinal sensitivity. No ocular or systemic side effects were detected. CONCLUSION: Anti-VEGF treatment of choroidal neovascularization in eyes with ARB resulted in anatomical changes that were only clinically significant in the eye with decreased visual acuity. The hyporeflective subretinal material remained unchanged suggesting a non-exudative cause. These findings provide new insights into the management of ARB, especially in pediatric subjects with CNV.

The MCP2 and the wrist plus two extensor compartments are the most affected and responsive joints/tendons out of the US7 score in patients with rheumatoid arthritis-an observational study.

BACKGROUND: There is no international consensus on an optimal ultrasound score for monitoring of rheumatoid arthritis (RA) on patient-level yet. Our aim was to reassess the US7 score for the identification of the most frequently pathologic and responsive joint/tendon regions, to optimize it and contribute to an international consensus. Furthermore, we aimed to evaluate the impact of disease duration on the performance of the score. METHODS: RA patients were assessed at baseline and after 3 and 6 months of starting/changing DMARD therapy by the US7 score in greyscale (GS) and power Doppler (PD). The frequency of pathologic joint/tendon regions and their responsiveness to therapy were analyzed by Friedman test and Cochrane-Q test respectively, including the comparison of palmar vs. dorsal regions (chi-square test). The responsiveness of different reduced scores and the amount of information retained from the original US7 score were assessed by standardized response means (SRM)/linear regression. Analyses were also performed separately for early and established RA. RESULTS: A total of 435 patients (N = 138 early RA) were included (56.5 (SD 13.1) years old, 8.2 (9.1) years disease duration, 80% female). The dorsal wrist, palmar MCP2, extensor digitorum communis (EDC) and carpi ulnaris (ECU) tendons were most frequently affected by GS/PD synovitis/tenosynovitis (wrist: 45%/43%; MCP2: 35%/28%; EDC: 30%/11% and ECU: 25%/11%) and significantly changed within 6 months of therapy (all p ≤0.003 by GS/PD). The dorsal vs. palmar side of the wrist by GS/PD (p < 0.001) and the palmar side of the finger joints by PD (p < 0.001) were more frequently pathologic. The reduced US7 score (GS/PD: palmar MCP2, dorsal wrist, EDC and ECU, only PD: dorsal MCP2) showed therapy response (SRM 0.433) after 6 months and retained 76% of the full US7 score's information. No major differences between the groups of early and established RA could be detected. CONCLUSIONS: The wrist, MCP2, EDC, and ECU tendons were most frequently pathologic and responsive to therapy in both early and established RA and should therefore be included in a comprehensive score for monitoring RA patients on patient-level.

Short-term outcomes in patients with center-involving diabetic macular edema after a single dose of intravitreal bevacizumab.

BACKGROUND: A significant portion of diabetic macular edema (DME) is refractory to anti-vascular endothelial growth factor (anti-VEGF) agents. This study investigates morphological and functional outcomes to a single intravitreal bevacizumab (IVB) injection in patients with center-involving DME (ciDME) at 4-6 weeks and compares treatment responders and non-responders based on spectral domain optical coherence tomography (SD-OCT) features. METHODS: IRB approved observational, retrospective chart review of patients with ciDME, identified by ICD-10 code, who received IVB and underwent baseline and 4-6 weeks follow-up SD-OCT imaging between January 1, 2016 and January 19, 2021. Patients who had received previous treatment with anti-VEGF or intraocular steroids within 1 year were excluded. Variables included best-corrected visual acuity (BCVA), central subfield thickness (CST) and total macular volume (TMV). Eyes were classified as responders if CST reduction was greater than 10%. OCT scans were graded qualitatively by two masked graders using Imagivault software. Paired Student's t-tests, Wilcoxon signed rank tests and Chi-Square tests were used for analysis. RESULTS: A total of 334 prospective subjects were identified, and after applying exclusion criteria 52 eyes from 46 patients (mean age 64.22 ± 8.12 years, 58.7% male) were included. Mean BCVA did not significantly change with treatment, 63.9 ETDRS letters (~ 20/50) at baseline and 65.9 ETDRS letters (~ 20/50) post-treatment (p = 0.07). Mean CST decreased from 466 ± 123 µm at baseline to 402 ± 86 µm post-treatment (p < 0.001). 22 (42.3%) of eyes were categorized as responders and 30 (57.7%) as non-responders. Average change in CST from baseline in responders was -164 µm (p < 0.001) and + 9 µm in non-responders (p = 0.47). Vitreomacular adhesion (VMA) was more prevalent in non-responders (28.7% vs. 4.8%, p = 0.03). In addition, cyst location in the inner nuclear layer (INL) was present more frequently in responders (95.5% vs. 73.3%, p = 0.037) as was subretinal fluid (45.5% vs. 13.3%, p = 0.01). CONCLUSION: The short-term response to a single IVB was sub-optimal with structural but no functional improvements. Greater baseline CST, presence of INL cysts and subretinal fluid may represent factors indicative of a better treatment response.

Retinal Thinning in People With Well-Controlled HIV Infection.

BACKGROUND: Retinal measurements correlate with disease progression in patients with multiple sclerosis; however, whether they associate with neurologic disease in people with controlled HIV is unknown. Using spectral domain optical coherence tomography, we evaluated retinal differences between people with HIV and HIV-negative controls and investigated clinical correlates of retinal thinning. METHODS: People with HIV on antiretroviral therapy for at least 1 year and HIV-negative controls recruited from the same communities underwent spectral domain optical coherence tomography, ophthalmic examination, brain MRI, and neuropsychological testing. Retinal nerve fiber layer (RNFL) and ganglion cell inner plexiform layer (GC-IPL) thicknesses were compared between groups using analysis of covariance with relevant clinical variables as covariates. Linear regression was used to explore associations of HIV history variables, cognitive domain scores, and MRI volume measurements within the HIV group. RESULTS: The HIV group (n = 69), with long-duration HIV infection (median time from diagnosis 19 years) and outstanding viral control have thinner retinal layers than HIV-negative controls (n = 28), after adjusting for covariates (GC-IPL: P = 0.002; RNFL: P = 0.024). The effect of HIV on GC-IPL thickness was stronger in women than in men (Women: P = 0.011; Men: P = 0.126). GC-IPL thickness is associated with information processing speed in the HIV group (P = 0.007, semipartial r = 0.309). No associations were found with retinal thinning and MRI volumes or HIV factors. CONCLUSIONS: People with HIV on antiretroviral therapy have thinning of the RNFL and GC-IPL of the retina, and women particularly are affected to a greater degree. This retinal thinning was associated with worse performance on tests of information processing speed.

Dynamics of human foveal development after premature birth.

PURPOSE: To determine the dynamic morphologic development of the human fovea in vivo using portable spectral domain-optical coherence tomography (SD-OCT). DESIGN: Prospective, observational case series. PARTICIPANTS: Thirty-one prematurely born neonates, 9 children, and 9 adults. METHODS: Sixty-two neonates were enrolled in this study. After examination for retinopathy of prematurity (ROP), SD-OCT imaging was performed at the bedside in nonsedated infants aged 31 to 41 weeks postmenstrual age (PMA) (= gestational age in weeks + chronologic age) and at outpatient follow-up ophthalmic examinations. Thirty-one neonates met eligibility criteria. Nine children and nine adults without ocular pathology served as control groups. Semiautomatic retinal layer segmentation was performed. Central foveal thickness, foveal to parafoveal (FP) ratio (central foveal thickness divided by thickness 1000 µm from the foveal center), and 3-dimensional thickness maps were analyzed. MAIN OUTCOME MEASURES: In vivo determination of foveal morphology, layer segmentation, analysis of subcellular changes, and spatiotemporal layer shifting. RESULTS: In contrast with the adult fovea, several signs of immaturity were observed in the neonates: a shallow foveal pit, persistence of inner retinal layers (IRLs), and a thin photoreceptor layer (PRL) that was thinnest at the foveal center. Three-dimensional mapping showed displacement of retinal layers out of the foveal center as the fovea matured and the progressive formation of the inner/outer segment band in the opposite direction. The FP-IRL ratios decreased as IRL migrated before term and minimally after that, whereas FP-PRL ratios increased as PRL subcellular elements formed closer to term and into childhood. A surprising finding was the presence of cystoid macular edema in 58% of premature neonates that appeared to affect inner foveal maturation. CONCLUSIONS: This study provides the first view into the development of living cellular layers of the human retina and of subcellular specialization at the fovea in premature infant eyes using portable SD-OCT. Our work establishes a framework of the timeline of human foveal development, allowing us to identify unexpected retinal abnormalities that may provide new keys to disease activity and a method for mapping foveal structures from infancy to adulthood that may be integral in future studies of vision and visual cortex development. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

Macular features from spectral-domain optical coherence tomography as an adjunct to indirect ophthalmoscopy in retinopathy of prematurity.

PURPOSE: To compare vitreoretinal pathology imaged with portable handheld spectral-domain optical coherence tomography (SD-OCT) to conventional indirect ophthalmoscopic examination in neonates undergoing screening for retinopathy of prematurity. METHODS: Spectral-domain optical coherence tomography images were collected from 76 eyes of 38 neonates during 118 routine retinopathy of prematurity examinations. Imaging sessions in the Neonatal Intensive Care Unit were performed immediately after the subjects underwent a standard ophthalmic examination with indirect ophthalmoscopic by a pediatric ophthalmologist. Masked certified SD-OCT graders evaluated scans for preretinal and retinal findings including material in the vitreous, epiretinal membrane, intraretinal cystoid structures and deposits, optic nerve and vascular features, and severity and location of retinopathy of prematurity. The frequency of detection of these features by clinical examination and evaluation of SD-OCT images was compared to determine potential clinical advantages for each modality. RESULTS: Portable SD-OCT imaging characterized macular features of retinal cystoid structures in 39% of examinations and epiretinal membrane in 32% of examinations. Neither feature was visualized by indirect ophthalmoscopy in any cases. The clinician using indirect ophthalmoscopy detected stage of retinopathy of prematurity and the presence or absence of Plus or pre-Plus disease. These were not visualized with SD-OCT. CONCLUSION: Spectral-domain optical coherence tomography provides new information about the premature infant retina that is of unknown importance relative to visual development and acuity. As used in this study, SD-OCT does not replace indirect ophthalmoscopy for evaluation of retinopathy of prematurity.

MULTIMODAL EVIDENCE OF TYPE 3 NEOVASCULARIZATION IN ENHANCED S-CONE SYNDROME.

PURPOSE: To investigate, using multimodal imaging, the anatomy of neovascularization in eyes with enhanced S-cone syndrome. METHODS: Three eyes with neovascularization, from two patients with enhanced S-cone syndrome, were analyzed using fluorescein angiography, indocyanine-green and optical coherence tomography angiography imaging. RESULTS: The eyes reported had a demonstrable Type 3 neovascularization with evidence of retinal-retinal anastomoses on fluorescein angiography, indocyanine-green and optical coherence tomography angiography imaging. One eye that was initially without neovascularization, but with chronic macular edema developed a macular hemorrhage. This eye was treated with 8 injections of intravitreal bevacizumab over 29-months resulting in a final fibrovascular lesion. The characteristics of this final lesion share similarities to the two other eyes described. In all eyes and all exams, retinal vessels are observed to communicate with the subretinal fibrovascular lesion. CONCLUSION: We provide evidence of retinal arteriovenous anastomosis of the superficial retinal plexus to a subretinal neovascular complex in patients with enhanced S-cone syndrome and point to similarities with Type 3 neovascularization in macular telengiectasia Type 2 (MacTel2) and age-related macular degeneration. These findings provide insights into the anatomy of neovascularization in these pathologies and may lead to hypotheses of their etiologies.

Acute-onset central serous retinopathy after immunization with COVID-19 mRNA vaccine.

PURPOSE: We report the case of a 33-year-old male who presented with unilateral central serous retinopathy three days after the injection of a COVID-19 vaccine. OBSERVATIONS: A 33-year-old healthy Hispanic male referred to the ophthalmology service due to blurry vision and metamorphopsia in the right eye without any flashes, floaters, eye redness or pain. The patient reported that 69 hours prior to presentation he received the first dose of the Pfizer-BioNTech BNT162b2 mRNA COVID-19 vaccine. He denied any past ocular history or pertinent medical history. He does not take any medicines and denies stressful factors in his life. The clinical examination and imaging tests were consistent with central serous retinopathy that resolved in three months. CONCLUSIONS AND IMPORTANCE: This is the first report of an ocular complication potentially associated with a COVID-19 vaccination. Our case contributes information of a side effect potentially related to this new vaccine.