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In 2017, ophthalmologists had a higher mean final MIPS score than both optometrists and all other physicians combined.

In an elegant example of bench-to-bedside research, a hypothesis that cells in the outflow pathway actively regulate conventional outflow resistance was proposed in the 1990s and systematically pursued, exposing novel cellular and molecular mechanisms of intraocular pressure (IOP) regulation. The critical discovery that pharmacologic manipulation of the cytoskeleton of outflow pathway cells decreased outflow resistance placed a spotlight on the Rho kinase pathway that was known to regulate the cytoskeleton. Ultimately, a search for Rho kinase inhibitors led to the discovery of several molecules of therapeutic interest, leaving us today with 2 new ocular hypotensive agents approved for clinical use: ripasudil in Japan and netarsudil in the United States. These represent members of the first new class of clinically useful ocular hypotensive agents since the US Food and Drug Administration approval of latanoprost in 1996. The development of Rho kinase inhibitors as a class of medications to lower IOP in patients with glaucoma and ocular hypertension represents a triumph in translational research. Rho kinase inhibitors are effective alone or when combined with other known ocular hypotensive medications. They also offer the possibility of neuroprotective activity, a favorable impact on ocular blood flow, and even an antifibrotic effect that may prove useful in conventional glaucoma surgery. Local adverse effects, however, including conjunctival hyperemia, subconjunctival hemorrhages, and cornea verticillata, are common. Development of Rho kinase inhibitors targeted to the cells of the outflow pathway and the retina may allow these agents to have even greater clinical impact. The objectives of this review are to describe the basic science underlying the development of Rho kinase inhibitors as a therapy to lower IOP and to summarize the results of the clinical studies reported to date. The neuroprotective and vasoactive properties of Rho kinase inhibitors, as well as the antifibrotic properties, of these agents are reviewed in the context of their possible role in the medical and surgical treatment of glaucoma.

Purpose To evaluate the long-term outcomes of rituximab (RTX) treatment in patients with ocular granulomatosis with polyangiitis (GPA) with localized or generalized disease. Design Retrospective cohort. Participants Thirty-seven patients with ocular GPA receiving RTX in a multidisciplinary vasculitis clinic between 2004 and 2013. Methods A total of 100 patients who received a course of RTX were identified, and notes were reviewed. Baseline demographic details, clinical characteristics (including organ involvement), drugs used, and outcome measures were recorded. Main Outcome Measures The percentage in remission (inactive disease with prednisolone ≤7.5 mg with or without maintenance treatment) at 6 months, time to remission, percentage relapsing, side effects, B-cell count, antineutrophil cytoplasm antibody titers, induction, and maintenance regimens. Results The median follow-up time after the first RTX course was 36.5 months. Twenty patients had scleritis, and 17 patients had orbital disease; 86% achieved remission at 6 months. The percentage in remission versus partial remission was not statistically significant between patients with scleritis and patients with orbital disease (85% vs. 15% with scleritis and 82% vs. 18% with orbital disease; P = 1.00). The percentage relapsing was not statistically significant ( P = 0.33) between scleritis (60%) and orbital disease (41%). Localized disease (ocular ± ear-nose-throat/lung) was observed in 57%, and generalized disease (ocular plus other organs) was observed in 43%, the former having a median duration of disease of 40 months. There was no statistically significant difference ( P = 0.37) in the percentage in remission between localized and generalized ocular disease. Relapses occurred in 51%, with localized disease being a significant risk factor for relapse. Fifty percent of patients with generalized disease versus none with localized disease received cyclophosphamide (CYP) as part of the induction regimen. Patients who received CYP during induction had significantly ( P = 0.027) lower ratios of baseline 12-month proteinase 3 titers than patients who did not have CYP. Infections were observed in 16% of patients, with 8% requiring hospital admission. Conclusions Our long-term data suggest that RTX is effective for inducing disease remission in localized and generalized ocular GPA. Localized disease is a significant risk factor for relapse, which may be related to less use of CYP in the induction regimen.

Purpose To describe the earliest features of ABCA4-associated retinopathy. Design Case series. Participants Children with a clinical and molecular diagnosis of ABCA4-associated retinopathy without evidence of macular atrophy. Methods The retinal phenotype was characterized by color fundus photography, OCT, fundus autofluorescence (FAF) imaging, electroretinography, and in 2 patients, adaptive optics scanning laser ophthalmoscopy (AOSLO). Sequencing of the ABCA4 gene was performed in all patients. Main Outcome Measures Visual acuity, OCT, FAF, electroretinography, and AOSLO results. Results Eight children with ABCA4-associated retinopathy without macular atrophy were identified. Biallelic variants in ABCA4 were identified in all patients. Four children were asymptomatic, and 4 reported loss of VA. Patients were young (median age, 8.5 years; interquartile range, 6.8 years) with good visual acuity (median, 0.155 logarithm of the minimum angle of resolution [logMAR]; interquartile range, 0.29 logMAR). At presentation, the macula appeared normal (n = 3), had a subtly altered foveal reflex (n = 4), or demonstrated manifest fine yellow dots (n = 1). Fundus autofluorescence identified hyperautofluorescent dots in the central macula in 3 patients, 2 of whom showed a normal fundus appearance. Only 1 child had widespread hyperautofluorescent retinal flecks at presentation. OCT imaging identified hyperreflectivity at the base of the outer nuclear layer in all 8 patients. Where loss of outer nuclear volume was evident, this appeared to occur preferentially at a perifoveal locus. Longitudinal split-detector AOSLO imaging in 2 individuals confirmed that the greatest change in cone spacing occurred in the perifoveal, and not foveolar, photoreceptors. Electroretinography showed a reduced B-wave–to–A-wave ratio in 3 of 5 patients tested; in 2 children, recordings clearly showed electronegative results. Conclusions In childhood-onset ABCA4-associated retinopathy, the earliest stages of macular atrophy involve the parafovea and spare the foveola. In some cases, these changes are predated by tiny, foveal, yellow, hyperautofluorescent dots. Hyperreflectivity at the base of the outer nuclear layer, previously described as thickening of the external limiting membrane, is likely to represent a structural change at the level of the foveal cone nuclei. Electroretinography suggests that the initial site of retinal dysfunction may occur after phototransduction.

To explore trends in the prevalence of self-reported visual impairment in the noninstitutionalized adult US population during the 27-year period from 1984 to 2010.Data obtained from the National Health Interview Survey (NHIS) and the Survey of Income and Program Participation (SIPP) were used to analyze trends in the prevalence of self-reported visual impairment in the United States.Representative, population-based samples of between 45 000 and 92 000 adults (NHIS) and between 37 000 and 71 000 adults (SIPP) during each year of data collection.Survey results were age-adjusted to a standard (2010) population. Sampling weights were used throughout the analysis using strata and primary sampling unit variables provided in the public use datasets to appropriately take into account the complex design of the surveys. The statistical significance of trends was estimated by computing the difference in chi-squares of a fit to a linear trendline and a fit without a trend.The trends and percent change in the prevalence of visual impairment from 1984 to 1996 and from 1997 to 2010 for NHIS and 1984 to 2010 for SIPP.On the basis of NHIS data, the prevalence of activity-limiting visual impairment among persons aged ≥65 years declined by 51.7% (P0.001), from 3.5% in 1984 to 1.7% in 1996, and by 45.8% (P0.001), from 3.1% in 1997 to 1.7% in 2010. On the basis of SIPP data, the prevalence of functional visual impairment in the same age category declined by 58.3% (P0.001), from 23.3% in 1984 to 9.7% in 2010, whereas the prevalence of severe functional impairment declined by 47.1% (P0.001), from 5.1% to 2.7%.There was a marked reduction in the prevalence of self-reported visual impairment in the noninstitutionalized adult US population during the period from 1984 to 2010.

To evaluate the long-term outcomes of rituximab (RTX) treatment in patients with ocular granulomatosis with polyangiitis (GPA) with localized or generalized disease.Retrospective cohort.Thirty-seven patients with ocular GPA receiving RTX in a multidisciplinary vasculitis clinic between 2004 and 2013.A total of 100 patients who received a course of RTX were identified, and notes were reviewed. Baseline demographic details, clinical characteristics (including organ involvement), drugs used, and outcome measures were recorded.The percentage in remission (inactive disease with prednisolone ≤7.5 mg with or without maintenance treatment) at 6 months, time to remission, percentage relapsing, side effects, B-cell count, antineutrophil cytoplasm antibody titers, induction, and maintenance regimens.The median follow-up time after the first RTX course was 36.5 months. Twenty patients had scleritis, and 17 patients had orbital disease; 86% achieved remission at 6 months. The percentage in remission versus partial remission was not statistically significant between patients with scleritis and patients with orbital disease (85% vs. 15% with scleritis and 82% vs. 18% with orbital disease; P = 1.00). The percentage relapsing was not statistically significant (P = 0.33) between scleritis (60%) and orbital disease (41%). Localized disease (ocular ± ear-nose-throat/lung) was observed in 57%, and generalized disease (ocular plus other organs) was observed in 43%, the former having a median duration of disease of 40 months. There was no statistically significant difference (P = 0.37) in the percentage in remission between localized and generalized ocular disease. Relapses occurred in 51%, with localized disease being a significant risk factor for relapse. Fifty percent of patients with generalized disease versus none with localized disease received cyclophosphamide (CYP) as part of the induction regimen. Patients who received CYP during induction had significantly (P = 0.027) lower ratios of baseline 12-month proteinase 3 titers than patients who did not have CYP. Infections were observed in 16% of patients, with 8% requiring hospital admission.Our long-term data suggest that RTX is effective for inducing disease remission in localized and generalized ocular GPA. Localized disease is a significant risk factor for relapse, which may be related to less use of CYP in the induction regimen.

Purpose To compare the results of Glaucoma Progression Analysis (GPA, Carl Zeiss Meditec, Dublin, CA) to subjective expert consensus in the detection of glaucomatous visual field progression. Design Retrospective, observational case series. Participants We included 100 eyes of 83 glaucoma patients. Methods Five serial Humphrey visual fields from 100 eyes of 83 glaucoma patients were evaluated by 5 masked glaucoma subspecialists for determination of progression. Four months later, with a randomly reordered patient sequence, the same visual field series were reevaluated by the same graders, at which time they had access to the Glaucoma Progression Analysis (GPA) printout. Main Outcome Measures The level of agreement between majority expert consensus and GPA, both before and after access to GPA data, was assessed using kappa statistics. Results On initial review and on reevaluation with access to the GPA printout, the level of agreement between majority expert consensus and GPA was fair (kappa = 0.52, 95% confidence interval [CI], 0.35–0.69 and kappa=0.62; 95% CI, 0.46–0.78, respectively). Expert consensus was more likely to classify a series of fields as showing progression than was GPA ( P ≤0.002). There was good agreement between expert consensus on initial review and reevaluation 4 months later (kappa = 0.77; 95% CI, 0.65–0.90). Conclusions The level of agreement between majority expert consensus of subjective determination of visual field progression and GPA is fair. In cases of disagreement with GPA, the expert consensus classification was usually progression. Access to the results of GPA did not significantly change the level of agreement between expert consensus and the GPA result; however, expert consensus did change in 11 of 100 cases. Financial Disclosure(s) Proprietary or commercial disclosure may be found after the references.

To determine the effect of cataract on the results of frequency-doubling technology (FDT) perimetry.Consecutive cohort study.Forty-four patients with normal ophthalmic examinations, with the exception of cataract, scheduled to undergo phacoemulsification and posterior chamber lens implantation were prospectively identified and completed the study.All subjects underwent FDT perimetry using the full-threshold C-20 strategy. Both eyes were tested within 1 month before cataract surgery and up to 3 months after surgery. The unoperated fellow eyes served as controls.Changes in visual acuity (VA), mean deviation (MD), and pattern standard deviation (PSD) were evaluated. For each subject, the change in MD and PSD in the eye that underwent cataract surgery was adjusted for change in the control eye that is thought to occur due to a learning effect.Among the eyes that underwent cataract surgery, the median preoperative VA was 20/60 (range, 20/30-20/800) and the mean preoperative MD was -4.00+/-3.72 decibels (dB). Postoperatively, the median VA improved to 20/30 (range, 20/20-20/70) and the mean postoperative MD was -0.26+/-3.09 dB (P0.001). Among the control eyes, MDs were -1.74+/-3.71 dB preoperatively and -0.94+/-3.85 dB postoperatively (P = 0.019). The adjusted improvement in MD among eyes that underwent cataract surgery was 2.94+/-3.44 dB (P0.001). There was no significant change in PSD. Preoperative VA correlated significantly with preoperative MD (r = 0.39, P = 0.01). The improvement in VA correlated significantly with the adjusted improvement in MD (r = 0.38, P = 0.01).Cataract has an adverse effect on the MD but not the PSD in FDT perimetry. Among eyes with visually significant cataract, the MD correlates significantly with VA. After cataract surgery, the change in VA correlates significantly with the adjusted change in MD.

Purpose To compare efficacies of adjunctive therapy with brimonidine 0.15% and adjunctive therapy with brinzolamide 1% in combination with travoprost 0.004%. Design Three-month randomized, parallel-group, double-masked, multicenter clinical trial. Participants Patients with primary open-angle glaucoma, exfoliation glaucoma, or ocular hypertension with intraocular pressure (IOP) > 18 mmHg on monotherapy with travoprost (N = 163). Methods Patients were randomized to receive adjunctive therapy with twice-daily brimonidine (N = 79) or twice-daily brinzolamide (N = 84). Treatment efficacy was assessed after 1 and 3 months of combination therapy. Intraocular pressure was measured at 8 am, noon, and 4 pm at baseline (on travoprost monotherapy) and after 3 months of combination therapy. Mean diurnal IOP was defined as the average of the IOP measurements at these 3 time points. Adverse events were recorded at each visit. Main Outcome Measure Difference between treatment groups in mean diurnal IOP at month 3, adjusted for difference in baseline IOP, using analysis of covariance. Results Mean diurnal IOPs (± standard error of the mean) at baseline were 21.7±0.33 mmHg in the brimonidine group and 21.1±0.29 mmHg in the brinzolamide group ( P = 0.16). Mean diurnal IOPs at month 3 were 19.6±0.41 mmHg in the brimonidine group and 18.4±0.33 mm Hg in the brinzolamide group ( P = 0.019). At month 3, mean diurnal IOPs, adjusted for difference in baseline IOP, were 19.3±0.27 in the brimonidine group and 18.6±0.25 in the brinzolamide group ( P = 0.035). Conclusions The combination of travoprost and brinzolamide was statistically significantly more efficacious than the combination of travoprost and brimonidine in lowering IOP. The clinical significance of this difference is uncertain.