Although there are many anecdotal reports of children with developmental dyslexia complaining of vision symptoms when reading, empirical studies are lacking. The primary aim of the present study was to document self-reported vision-related symptoms in children with developmental dyslexia and typically reading peers. We also explored whether vision symptoms were correlated with sensorimotor measures of vergence, accommodation and ocular motor tracking skills. Using a prospective group comparison observational design, we assessed 28 children with developmental dyslexia (DD) and 33 typically reading children (TR) 7-11 years of age. Participants completed psychoeducational testing, a comprehensive sensorimotor eye examination, and the Convergence Insufficiency Symptom Survey (CISS), which includes 9 items pertaining to vision-related symptoms (CISS-V) and 6 that could have cognitive influence (CISS-C). CISS-V were significantly greater in DD than TR children. Ocular motor tracking, assessed by an infra-red limbal eye tracker while reading text, was most clearly associated with the visual symptoms, but only within the DD group. Vision-related symptom surveys followed by a comprehensive eye examination with detailed evaluation of sensorimotor functioning for those who report a high prevalence of symptoms may be clinically relevant for children with DD.

Pigmentary glaucoma (PG) is a common glaucoma subtype that results from release of pigment from the iris, called pigment dispersion syndrome (PDS), and its deposition throughout the anterior chamber of the eye. Although PG has a substantial heritable component, no causative genes have yet been identified. We used whole exome sequencing of two independent pedigrees to identify two premelanosome protein (PMEL) variants associated with heritable PDS/PG. PMEL encodes a key component of the melanosome, the organelle essential for melanin synthesis, storage and transport. Targeted screening of PMEL in three independent cohorts (n = 394) identified seven additional PDS/PG-associated non-synonymous variants. Five of the nine variants exhibited defective processing of the PMEL protein. In addition, analysis of PDS/PG-associated PMEL variants expressed in HeLa cells revealed structural changes to pseudomelanosomes indicating altered amyloid fibril formation in five of the nine variants. Introduction of 11-base pair deletions to the homologous pmela in zebrafish by the clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9 method caused profound pigmentation defects and enlarged anterior segments in the eye, further supporting PMEL's role in ocular pigmentation and function. Taken together, these data support a model in which missense PMEL variants represent dominant negative mutations that impair the ability of PMEL to form functional amyloid fibrils. While PMEL mutations have previously been shown to cause pigmentation and ocular defects in animals, this research is the first report of mutations in PMEL causing human disease.

PURPOSE: To compare the rates of infectious endophthalmitis following intravitreal injection of ranibizumab using prefilled syringes vs conventional preparation. DESIGN: Multicenter retrospective cohort study. METHODS: All eyes receiving intravitreal injection of 0.5 mg ranibizumab for retinal vascular diseases at 10 retina practices across the United States (2016 to 2017) and Japan (2009 to 2017) were included. The total numbers of eyes and injections were determined from billing codes. Endophthalmitis cases were determined from billing records and evaluated with chart review. Primary outcome was the rate of postinjection acute endophthalmitis. Secondary outcomes were visual acuity and microbial spectrum. RESULTS: A total of 243 754 intravitreal 0.5 mg ranibizumab injections (165 347 conventional and 78 407 prefilled) were administered to 43 132 unique patients during the study period. In the conventional ranibizumab group, a total of 43 cases of suspected endophthalmitis occurred (0.026%; 1 in 3845 injections) and 22 cases of culture-positive endophthalmitis occurred (0.013%; 1 in 7516 injections). In the prefilled ranibizumab group, 12 cases of suspected endophthalmitis occurred (0.015%; 1 in 6534 injections) and 2 cases of culture-positive endophthalmitis occurred (0.0026%; 1 in 39 204 injections). Prefilled syringes were associated with a trend toward decreased risk of suspected endophthalmitis (odds ratio 0.59; 95% confidence interval 0.31-1.12; P = .10) and a statistically significant decreased risk of culture-positive endophthalmitis (odds ratio 0.19; 95% confidence interval 0.045-0.82; P = .025). Average logMAR vision loss at final follow-up was significantly worse for eyes that developed endophthalmitis from the conventional ranibizumab preparation compared to the prefilled syringe group (4.45 lines lost from baseline acuity vs 0.38 lines lost; P = .0062). Oral-associated flora was found in 27.3% (6/22) of conventional ranibizumab culture-positive endophthalmitis cases (3 cases of Streptococcus viridans, 3 cases of Enterococcus faecalis) compared to 0 cases in the prefilled ranibizumab group. CONCLUSION: In a large, multicenter, retrospective study the use of prefilled syringes during intravitreal injection of ranibizumab was associated with a reduced rate of culture-positive endophthalmitis, including from oral flora, as well as with improved visual acuity outcomes.

BACKGROUND: To assess prevalence and causes of vision loss in Central and South Asia. METHODS: A systematic review of medical literature assessed the prevalence of blindness (presenting visual acuity<3/60 in the better eye), moderate and severe vision impairment (MSVI; presenting visual acuity <6/18 but ≥3/60) and mild vision impairment (MVI; presenting visual acuity <6/12 and ≥6/18) in Central and South Asia for 1990, 2010, 2015 and 2020. RESULTS: In Central and South Asia combined, age-standardised prevalences of blindness, MSVI and MVI in 2015 were for men and women aged 50+years, 3.72% (80% uncertainty interval (UI): 1.39-6.75) and 4.00% (80% UI: 1.41-7.39), 16.33% (80% UI: 8.55-25.47) and 17.65% (80% UI: 9.00-27.62), 11.70% (80% UI: 4.70-20.32) and 12.25% (80% UI:4.86-21.30), respectively, with a significant decrease in the study period for both gender. In South Asia in 2015, 11.76 million individuals (32.65% of the global blindness figure) were blind and 61.19 million individuals (28.3% of the global total) had MSVI. From 1990 to 2015, cataract (accounting for 36.58% of all cases with blindness in 2015) was the most common cause of blindness, followed by undercorrected refractive error (36.43%), glaucoma (5.81%), age-related macular degeneration (2.44%), corneal diseases (2.43%), diabetic retinopathy (0.16%) and trachoma (0.04%). For MSVI in South Asia 2015, most common causes were undercorrected refractive error (accounting for 66.39% of all cases with MSVI), followed by cataract (23.62%), age-related macular degeneration (1.31%) and glaucoma (1.09%). CONCLUSIONS: One-third of the global blind resided in South Asia in 2015, although the age-standardised prevalence of blindness and MSVI decreased significantly between 1990 and 2015.

To identify genetic variants associated with diabetic retinopathy (DR), we performed a large multiethnic genome-wide association study. Discovery included eight European cohorts ( = 3,246) and seven African American cohorts ( = 2,611). We meta-analyzed across cohorts using inverse-variance weighting, with and without liability threshold modeling of glycemic control and duration of diabetes. Variants with a value <1 × 10 were investigated in replication cohorts that included 18,545 European, 16,453 Asian, and 2,710 Hispanic subjects. After correction for multiple testing, the C allele of rs142293996 in an intron of nuclear VCP-like () was associated with DR in European discovery cohorts ( = 2.1 × 10), but did not reach genome-wide significance after meta-analysis with replication cohorts. We applied the Disease Association Protein-Protein Link Evaluator (DAPPLE) to our discovery results to test for evidence of risk being spread across underlying molecular pathways. One protein-protein interaction network built from genes in regions associated with proliferative DR was found to have significant connectivity ( = 0.0009) and corroborated with gene set enrichment analyses. These findings suggest that genetic variation in as well as variation within a protein-protein interaction network that includes genes implicated in inflammation, may influence risk for DR.

PURPOSE: To evaluate the durability of diabetic retinopathy (DR) improvements after a change in ranibizumab dosing from monthly to individualized pro re nata (PRN) therapy. DESIGN: Pooled analysis of the open-label extension (OLE) of RIDE and RISE (clinicaltrials.gov identifiers, NCT00473382 and NCT00473330) patients with DR and diabetic macular edema (DME). PARTICIPANTS: Patients who completed 36-month participation in RIDE and RISE and entered the OLE. METHODS: In RIDE and RISE, patients (n = 759) were randomized 1:1:1 to ranibizumab 0.3 mg monthly, 0.5 mg monthly, or monthly sham injections with rescue macular laser available after 6 months, per protocol-specified criteria. After 24 months, sham patients crossed over to ranibizumab 0.5 mg monthly. After 36 months in the core studies, patients in the OLE (n = 500) could receive ranibizumab 0.5 mg PRN based on predefined DME re-treatment criteria. Diabetic retinopathy severity was evaluated photographically using the Early Treatment Diabetic Retinopathy Study DR severity scale. MAIN OUTCOME MEASURES: Change in DR severity from months 36 to 48 by re-treatment status. RESULTS: Among patients who entered the OLE, 121 of 500 (24%) did not require additional ranibizumab injections. Overall, 367 patients had evaluable DR at months 36 and 48. Among patients not requiring ranibizumab re-treatment from months 36 to 48 (88/367), 57% to 78%, 0% to 7%, and 22% to 36% experienced DR severity stability, 2-step or more improvement, and 2-step or more worsening, respectively. Among patients requiring ranibizumab re-treatment (279/367), 84% to 94%, 2%, and 3% to 14% experienced DR severity stability, 2-step or more improvement, and 2-step or more worsening, respectively. On average, vision improvements were maintained during the OLE regardless of change in DR severity. CONCLUSIONS: Diabetic retinopathy severity improvements with ranibizumab were maintained in over 70% of OLE patients after switching from ranibizumab monthly to an individualized ranibizumab 0.5 mg PRN dosing regimen. Because approximately one third of OLE patients experienced DR worsening, careful monitoring should be part of the long-term management of patients with DR.

PURPOSE: To review the published evidence to evaluate the ability of orthokeratology (Ortho-K) treatment to reduce myopic progression in children and adolescents compared with the use of spectacles or daytime contact lenses for standard refractive correction. METHODS: Literature searches of the PubMed database, the Cochrane Library, and the databases of clinical trials were last conducted on August 21, 2018, with no date restrictions but limited to articles published in English. These searches yielded 162 citations, of which 13 were deemed clinically relevant for full-text review and inclusion in this assessment. The panel methodologist then assigned a level of evidence rating to the selected studies. RESULTS: The 13 articles selected for inclusion include 3 prospective, randomized clinical trials; 7 nonrandomized, prospective comparative studies; and 3 retrospective case series. One study provided level I evidence, 11 studies provided level II evidence, and 1 study provided level III evidence. Most studies were performed in populations of Asian ethnicity. Change in axial length was the primary outcome for 10 of 13 studies and change in refraction was the primary outcome for 3 of 13 studies. In these studies, Ortho-K typically reduced axial elongation by approximately 50% over a 2-year study period. This corresponds to average axial length change values of approximately 0.3 mm for Ortho-K patients compared with 0.6 mm for control patients, which corresponds to a typical difference in refraction of approximately 0.5 diopters (D). Younger age groups and individuals with larger than average pupil size may have a greater effect with Ortho-K. Rebound can occur after discontinuation or change to alternative refractive treatment. CONCLUSIONS: Orthokeratology may be effective in slowing myopic progression for children and adolescents, with a potentially greater effect when initiated at an early age (6-8 years). Safety remains a concern because of the risk of potentially blinding microbial keratitis from contact lens wear.

High levels of proinflammatory cytokines have been associated with a loss of tissue function in ocular autoimmune diseases, but the basis for this relationship remains poorly understood. Here we investigate a new role for tumor necrosis factor α in promoting N-glycan-processing deficiency at the surface of the eye through inhibition of N-acetylglucosaminyltransferase expression in the Golgi. Using mass spectrometry, complex-type biantennary oligosaccharides were identified as major N-glycan structures in differentiated human corneal epithelial cells. Remarkably, significant differences were detected between the efficacies of cytokines in regulating the expression of glycogenes involved in the biosynthesis of N-glycans. Tumor necrosis factor α but not IL-1β had a profound effect in suppressing the expression of enzymes involved in the Golgi branching pathway, including N-acetylglucosaminyltransferases 1 and 2, which are required for the formation of biantennary structures. This decrease in gene expression was correlated with a reduction in enzymatic activity and impaired N-glycan branching. Moreover, patients with ocular mucous membrane pemphigoid were characterized by marginal N-acetylglucosaminyltransferase expression and decreased N-glycan branching in the conjunctiva. Together, these data indicate that proinflammatory cytokines differentially influence the expression of N-glycan-processing enzymes in the Golgi and set the stage for future studies to explore the pathophysiology of ocular autoimmune diseases.

PURPOSE: To report the long-term outcome of Prosthetic Replacement of the Ocular Surface Ecosystem (PROSE) for delivery of bevacizumab in the treatment of corneal neovascularization (KNV). METHODS: Retrospective, non-comparative, interventional case series of 13 sequential patients treated for KNV at the BostonSight between 2006 and 2017. In all cases, PROSE treatment was initiated for management of ocular surface disease and patients wore PROSE consistently on a daily wear basis prior to bevacizumab treatment. Patients applied a drop of 1% preservative free bevacizumab to the reservoir of PROSE device twice daily. Patients continued with daily wear of the device during treatment and afterwards. RESULTS: 13 patients (8 female and mean age of 45 years) are included with a mean follow-up of 5.1 years (range 6 months-11 years). Underlying ocular diagnoses included Stevens-Johnson syndrome (7), ocular chronic graft-versus-host disease (2), corneal transplant (2), contact lens-related corneal ulcer and limbal stem cell deficiency (1), and familial dysautonomia (1). Median duration of bevacizumab use was 6 months (range 3 months-10 years). Twelve cases (92%) had regression of KNV and 10 cases (77%) had improved best-corrected visual acuity (BCVA) with treatment. Median BCVA improved from -1.1 (LogMAR) at baseline, to -0.66 at end of bevacizumab treatment, and remained -0.63 at last follow-up (P = 0.047). KNV progressed in one eye after discontinuation of bevacizumab. There were no ophthalmic or systemic complications. CONCLUSIONS: Topical bevacizumab used in PROSE is effective in treating KNV and improving vision. Long-term follow-up reveals durable response and no complications.

PURPOSE: To assess the effect of intravitreal injections of anti-vascular endothelial growth factor (VEGF) agents on immediate and long-term intraocular pressure (IOP) elevation and glaucoma. METHODS: Literature searches of the PubMed and Cochrane databases, last conducted in April 2018, yielded 253 unique citations. Of these, 41 met the inclusion criteria and were rated according to the strength of evidence. Two articles were rated level I, 17 were rated level II, and 15 were rated level III; an additional 7 were excluded because of poor study design and lack of relevance to the topic under evaluation. RESULTS: The studies that reported on short-term IOP elevation (i.e., between 0 and 60 minutes) showed that an immediate increase in IOP is seen in all patients when measured between 0 and 30 minutes of intravitreal injection and that the IOP elevation decreases over time. The data on long-term IOP elevation were mixed; 7 studies reported that between 4% and 15% of patients developed sustained elevation of IOP at 9 to 24 months after injection, whereas 6 studies found no long-term change in IOP from 1 to 36 months after injection. Pretreatment with glaucoma medications, anterior chamber tap, vitreous reflux, longer intervals between injections, and longer axial lengths were associated with lower IOP elevations after injection. Data were mixed on the relationship between IOP increase and the type of intravitreal injection, number of intravitreal injections, preexisting glaucoma, and globe decompression before injection. There were no data on the onset or progression of glaucoma in the studies reviewed in this assessment. CONCLUSIONS: Intravitreal injection of anti-VEGF agents results in an immediate and transient increase in IOP. A long-term increase in IOP also may be seen, and further studies are needed to determine at-risk populations. Although there is some suggestion in the literature, there is currently insufficient data to determine the impact of intravitreal anti-VEGF injections on glaucoma progression. Although pretreatment with glaucoma medications, performing anterior chamber paracentesis, or increasing the interval between injections may reduce the impact of transient IOP elevation, the clinical significance and associated risks of these interventions are unknown.