Off the Cuff: Red Herring

Olopatadine HCl is an anti-allergy drug used for the management of allergic conjunctivitis. Currently, it is delivered via an eye drop solution, which is highly inefficient due to low bioavailability. Silicone contact lenses can be used to sustain the release of ophthalmic drugs. However, the presence of drugs alters the optical transmittance and physical properties of the contact lens. The objective was to design a novel PVP (polyvinyl pyrrolidone)-coated olopatadine-ethyl cellulose microparticles laden doughnut contact lens to sustained ocular delivery with limited alteration to the optical and swelling properties of the contact lens. The doughnut was implanted within the periphery of the lens using a modified casting technique. Olopatadine HCl was loaded by soaking (SM-OL), direct loading (DL-OL) and the doughnut casting method (DNT-OL). PVP (comfort agent) was loaded on the surface of contact lens for all the batches via a novel curing technique.

The in vitro olopatadine HCl release data of SM-OL (up to 48 to 72 hours) and DL-OL batches (up to 72 hours) showed high-burst release, while the DNT-OL batch showed sustained release up to 120 hours without significant (p>0.05) alteration in the optical and swelling properties of the contact lens. All the batches showed sustained release of PVP up to 120 hours. The in vivo studies in the rabbit tear fluid showed improvement in the olopatadine HCl and PVP retention time in comparison to eye drop solution. The PVP-loaded DNT-OL-500 lens showed tear stabilization (comfort wear) in Schirmer’s strip tests (rabbits) with no protein adherence in comparison to the DNT-OL-500 lens without PVP.

The study demonstrated the successful delivery of olopatadine HCl and PVP-K30 from the doughnut contact lens for the extended period of time with limited alteration to the optical and swelling properties of contact lens.

These researchers evaluated the efficacy of repeat selective laser trabeculoplasty (SLT) in medication-naive open-angle glaucoma (OAG) and ocular hypertensive (OHT) patients requiring repeat treatment for early to medium-term failure during the Laser in Glaucoma and Ocular Hypertension (LiGHT) trial, as part of a post hoc analysis of the SLT treatment arm of a multicenter, prospective, randomized controlled trial. Included were participants with treatment-naive OAG or OHT requiring repeat 360-degree SLT within 18 months. Retreatment was triggered by predefined IOP and disease-progression criteria (using objective individualized target IOPs). After SLT at baseline, patients were followed for a minimum of 18 months after a second (repeat) SLT. A mixed-model analysis was performed with the eye as the unit of analysis, with crossed random effects to adjust for correlation between fellow eyes and repeated measures within eyes. Kaplan-Meier curves helped plot the duration of effect. Main outcome measures were initial (early) IOP lowering at two months, and duration of effect after initial and repeat SLT.

A total of 115 eyes of 90 patients received repeat SLT during the first 18 months of the trial. Pretreatment IOP before initial SLT was significantly higher than before retreatment IOP of repeat SLT. Absolute IOP reduction at two months was greater after initial SLT compared with repeat SLT. Adjusted absolute IOP reduction at two months (adjusting for IOP before initial or repeat laser) was greater after repeat SLT. A total of 34 eyes were early failures (retreatment two months after initial SLT) vs. 81 later failures (retreatment >2 months after initial SLT). No significant difference in early absolute IOP reduction at two months after repeat SLT was noted between early and later failures. Repeat SLT maintained drop-free IOP control in 67% of 115 eyes at 18 months, with no clinically relevant adverse events.

These exploratory analyses demonstrated that repeat SLT could maintain IOP at or below target IOP in medication-naive OAG and OHT eyes requiring retreatment with at least an equivalent duration of effect to initial laser.

Mechanisms behind pigmentary glaucoma, a form of early-onset glaucoma that may potentially lead to severe visual impairment or blindness, are poorly understood. Researchers attempted to calculate the single-nucleotide polymorphism (SNP) heritability of pigmentary glaucoma and identify genetic associations with the disease. This genome-wide association study included affected individuals from Germany and control participants from the United Kingdom. Genome-wide information was obtained for patients with pigmentary glaucoma and control participants free of glaucoma by using the Illumina Human Omni Express Exome 8 v1.2 chip and genomic imputation. The SNP heritability of pigmentary glaucoma was estimated through a restricted maximum likelihood analysis. Associations between the genetic variants, and pigmentary glaucoma obtained from age, sex and principal component-adjusted logistic regression models were compared with those of SNPs previously associated with other eye phenotypes using Pearson product-moment correlations. Data were collected from November 2008 to January 2018, and analysis was completed between April 2018 and August 2019. An estimate of SNP-explained heritability for pigmentary glaucoma; correlations of effect sizes between pigmentary glaucoma, iris pigmentation and myopia; and correlations of effect sizes between pigmentary glaucoma and other eye phenotypes.

A total of 227 affected individuals (mean [SD] age, 58.7 [13.3] years) and 291 control participants (mean [SD] age, 80.2 [4.9] years) were included; all were of European ancestry. The SNP heritability of pigmentary glaucoma was 0.45. Twelve SNPs previously reported with genome-wide significant associations with eye pigmentation were associated with pigmentary glaucoma's SNP heritability (4.9% SNP heritability). Pigmentary glaucoma SNP effect sizes were correlated moderately for myopia and more strongly with those for iris pigmentation, although this was nonsignificant per a strict adjusted significance threshold.

These findings supported the conclusion that pigmentary glaucoma may have a genetic basis and be highly heritable. Variants associated with lighter eye color and myopia appear to be associated with increased risk of pigmentary glaucoma, but no shared genetic basis with primary open-angle glaucoma (or its quantitative endophenotype of cup-disc ratio) was observed.