Pepose Vision Institute

PurposeTo compare the effect of faricimab, a dual angiopoietin-2 (Ang-2) and VEGF-A inhibitor, with aflibercept on resolution of hyperreflective foci (HRF) in patients with diabetic macular edema (DME).DesignA post hoc analysis of the randomized, double-masked, noninferiority YOSEMITE/RHINE (NCT03622580/NCT03622593) phase III trials.ParticipantsAdults with vision loss due to center-involving DME.MethodsA deep learning–based algorithm was used to automatically quantify HRF in spectral-domain OCT volume scans from YOSEMITE/RHINE. Study eyes were randomized to faricimab 6.0 mg every 8 weeks (Q8W; n = 519), faricimab 6.0 mg according to a personalized treat-and-extend (T&E)–based regimen (n = 524), and aflibercept 2.0 mg Q8W (n = 502). Hyperreflective foci were defined as hyperreflective objects up to 50 μm in diameter and assessed within the 1.0-mm and 3.0-mm–diameter ETDRS rings and by location within the inner and outer retina.Main Outcome MeasuresHyperreflective foci volume and count at baseline and over time through week 48 in the inner, outer, and total retina, 1-mm and 3-mm diameters; time to absence of HRF at 2 consecutive visits in the inner and outer retina, 1-mm diameter over 48 weeks.ResultsAdjusted mean HRF volumes at week 48 were lower for faricimab Q8W (104.1 picoliter [pL]) and faricimab T&E (110.1 pL) compared with aflibercept (180.3 pL; nominal P < 0.001 for both) in the inner retina, 1-mm diameter. In the inner retina, 3-mm diameter adjusted mean HRF volumes at week 48 were lower for faricimab Q8W (763.9 pL) and faricimab T&E (777.2 pL) compared with aflibercept (1030.6 pL; nominal P < 0.001 for both). Similar results were obtained for volumes in the outer retina and for HRF counts. In the inner retina, 1-mm diameter, the 25th percentile for time to absence of HRF count at 2 consecutive visits was achieved 8 weeks earlier with faricimab Q8W and faricimab T&E versus aflibercept.ConclusionsGreater HRF reductions were achieved with faricimab versus aflibercept, supporting the therapeutic potential of dual Ang-2/VEGF-A inhibition to suppress disease activity in DME.Financial Disclosure(s)Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Purpose: To investigate how home optical coherence tomography (OCT) influences the clinical decision-making of retina specialists for the management of neovascular age-related macular degeneration (nAMD). Methods: In this retrospective imaging review, 15 retina specialists each evaluated 10 home OCT data segments from 29 eyes being treated for nAMD. Based on OCT data, indications were identified for when eyes should be treated, which antivascular endothelial growth factor should be used, and the specific retinal fluid and time thresholds for notification. Results: Withholding treatment was recommended in 64 (42.7%) of 150 data segments (95% CI, 34.7-50.6), whereas 100% of eyes received treatment on the last day of each data segment. Treatment was recommended in 86 cases (57.3%), with treatment occurring 7 or more days before the actual treatment was advised in 52 (60.5%) of 86 data segments. This earlier treatment would have prevented the accumulation of intraretinal fluid (IRF), subretinal fluid (SRF), and total retinal fluid for 69.1 nL, 162.2 nL, and 231.2 nL days. Retina specialists chose a different type of treatment agent in 35 (40%) of 86 cases. The following notification values were set: IRF, mean 9.8 ± 14.9 nL (median, 5; IQR, 5); SRF, mean 10.2 ± 16.1 nL (median, 5.5; IQR, 5); total retinal fluid, mean 15.2 ± 24.0 nL (median, 10; IQR, 5). The time-based notification interval was set at a mean of 34.7 ± 21.9 days (median, 30; IQR, 2). Conclusions: Home OCT-based decision-making by retina specialists differed substantially from actual clinical care. Home OCT has the potential to facilitate personalized care in nAMD.

PurposeDim light vision disturbances (DLD) comprise a wide range of symptoms affecting the quality of vision at low illumination including glare, halos, and starbursts. This exploratory study investigated 1.0% phentolamine mesylate ophthalmic solution (PMOS) as a treatment to improve vision and image quality for patients with DLD.MethodsIn this placebo-controlled, randomized, double-masked clinical trial, 24 adult patients with severe DLD were randomized in a 2:1 ratio to receive either one dose of PMOS or placebo. Subjects were eligible if they reported experiencing severe night vision difficulty that was not eliminated by distance spectacle correction and scored ≥0.3 log units below the normal range of contrast sensitivity assessed under mesopic conditions with glare at ≥2 spatial frequencies. Key efficacy outcomes were change from baseline in pupil diameter, contrast sensitivity, and visual acuity. Safety measures including intraocular pressure, conjunctival hyperemia, and systemic effects were also assessed.ResultsEight subjects were randomized to placebo (63% female; mean age 47 years) and 16 were randomized to PMOS (75% female; mean age 42 years). Mean (SD) pupil diameter of PMOS-treated subjects decreased significantly − 1.3 mm (0 to − 2.8 mm) with p < 0.0001. Mean contrast sensitivity with glare in PMOS-treated subjects improved significantly post-treatment at spatial frequencies 3, 6, 12, and 18 cycles per degree (p ≤ 0.03). PMOS also demonstrated improvements in the numbers of letters read for mesopic and photopic, high- and low-contrast visual acuity (LCVA). Importantly, a statistically greater proportion of PMOS-treated eyes registered mesopic LCVA 5 letter (69% vs. 31%, p = 0.029) and 10 letter (34% vs. 6%, p = 0.04) improvement, with a trend at 15 letters (19% vs. 0%, p = 0.16). PMOS was well tolerated with the only reported side effect being a mild increase in conjunctival hyperemia.ConclusionPMOS was well tolerated and effectively reduced pupil size with improvements in contrast sensitivity and visual acuity in adults with severe DLD. Future Phase 3 studies should be conducted to further evaluate its potential to treat DLD.Trial registrationThe trial registration number is NCT04004507 (02/07/2019). Retrospectively registered.

After a dilated eye examination, many patients experience symptoms of prolonged light sensitivity, blurred vision, and cycloplegia associated with pharmacological mydriasis. Phentolamine mesylate ophthalmic solution (PMOS) may expedite the reversal of mydriasis in patients, potentially facilitating return to functional vision and reducing barriers to obtaining dilated eye examinations. The protracted reversal time after pharmacologically induced pupil dilation impairs vision. We tested the hypothesis that PMOS rapidly reduces pupil diameter in this acute indication. In this double-masked placebo-controlled, randomized, two-arm crossover phase 2b trial, we evaluated the effects of one drop of 1% PMOS applied bilaterally in subjects who had their pupils dilated by one of two common mydriatic agents: 2.5% phenylephrine or 1% tropicamide. End points included change in pupil diameter, percent of subjects returning to baseline pupil diameter, and accommodative function at multiple time points. Thirty-one subjects completed the study (15 dilated with phenylephrine and 16 with tropicamide). Change in pupil diameter from baseline at 2 hours after maximal dilation with 1% PMOS was -1.69 mm and was significantly greater in magnitude compared with placebo for every time point beyond 30 minutes (P < .05). At 2 hours, a greater percentage of study eyes given 1% PMOS returned to baseline pupil diameter compared with placebo (29 vs. 13%, P = .03), which was this also seen at 4 hours (P < .001). More subjects treated with PMOS in the tropicamide subgroup had at least one eye returning to baseline accommodative amplitude at 2 hours (63 vs. 38%, P = .01). There were no severe adverse events, with only mild to moderate conjunctival hyperemia that resolved in most patients by 6 hours. Phentolamine mesylate ophthalmic solution at 1% reversed medically induced pupil dilation more rapidly than placebo treatment regardless of which mydriatic was used (adrenergic agonists and cholinergic blockers) with a tolerable safety profile.

PurposeTo assess the direct and indirect costs of infectious conjunctivitis and quantify medical costs due to conjunctivitis transmission in families.MethodsIn this retrospective claims analysis from the OptumHealth Care Solutions, Inc. database (1998–2016), beneficiaries with or without at least one diagnosis of infectious conjunctivitis were identified. Direct and indirect costs (in 2016 US$) during the 60 days post conjunctivitis diagnosis (or imputed date for controls) were compared using cost differences in linear regressions. For transmission cost analysis, the total cost of each conjunctivitis episode was the sum of the primary episode (seed patient) and the secondary episode (infected family members) costs. A generalized estimating equation model adjusted for seed patient characteristics was used to assess the impact of number and rate of transmissions on episode cost.ResultsHealth care resource utilization and direct costs were significantly higher for patients with conjunctivitis (n=1,002,188) versus controls (n=4,877,210): 1.67 all-cause visits per person per month (PPPM) versus 0.79 visits PPPM, respectively; total mean direct cost of $396.04 PPPM versus $289.63 PPPM, respectively. The cost of medically related absenteeism was $105.42 (95% confidence interval [CI], $104.18–$106.75) higher for patients with conjunctivitis than for controls. Episode cost, without transmission due to seed patient, was $669.43 (95% CI, $654.67–$684.85); it increased with each additional infected family member and with increased infection transmission time between family members.ConclusionConjunctivitis was associated with a notable economic burden in terms of direct medical costs and medically related absenteeism. Family health care costs increased with transmission time and with each family member infected with conjunctivitis.