Faculty Bibliography

PURPOSE/OBJECTIVE:Dim 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. METHODS:In 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. RESULTS:Eight 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. CONCLUSION/CONCLUSIONS:PMOS 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 REGISTRATION/BACKGROUND:The trial registration number is NCT04004507 (02/07/2019). Retrospectively registered.

There are close to two billion individuals globally living with presbyopia. In spite of its ubiquitous and progressive nature, there is no widely accepted, formal guideline or consensus statement on the classification of presbyopia by degree of severity. A panel of leading eye care professionals representing both optometrists and ophthalmologists convened virtually to discuss and document their combined assessments from the body of literature and clinical practice expertise in this commentary. In light of emerging therapies, classifying presbyopia by mild, moderate, or advanced severity may help provide consistency of diagnosis among eye care providers and may aid in managing patient expectations with different treatment options.

Objectives: Undergraduate college courses on well-being have proliferated in the United States, but there are few data examining whether they have an impact on student well-being or mental health. This study examined the impact of such a course on students' well-being and grade point average (GPA) compared to students who completed a psychology course on psychopathology.
Method(s): Participants were 152 undergraduates enrolled in the "Science of Happiness" (SOH), which focuses on well-being and mental health challenges (n = 64), and "Child and Adolescent Psychopathology" (CAP), a psychology course (n = 88). Well-being measures were collected using validated questionnaires (PERMA Profiler [PP], Satisfaction with Life Scale [SWLS]) at the beginning of the semester and at the completion of the semester. Both t tests and linear regression examined the effect of the courses on the outcomes.
Result(s): At baseline, there were no statistically significant differences in well-being or grades between the 2 groups. Examining the pre/post-SOH changes, we found statistically significant improvements on the SWLS (M = 1.28; SD = 4.85; t63 = 2.11; p < 0.04) and in GPA (M = 0.07; SD = 0.17; t72 = 3.47; p < 0.001). The improvement in the PP Well-being was not significant for either SOH or CAP but trended positive for SOH (M = 0.05) and negative for CAP (M = -0.05). In CAP, there was no statistically significant improvement in SWLS, but GPA change was statistically significant (M = 0.04; SD = 0.14; t96 = 2.99; p < 0.004). When we examined the pre-/postdifferences between the 2 groups, we found no statistical significance for SWLS or GPA.
Conclusion(s): Given the prevalence of mental health challenges in college students and the need for effective, large-scale prevention interventions for this population, courses on well-being are a strategy that warrant further exploration. PRE, COLST, SC
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The purpose of this article is to review the current status of presbyopia amelioration with surgical and pharmacologic procedures that partially compensate for loss of accommodation in advance of cataract surgery and lens replacement. Over the last few years, several corneal surgical and topical pharmacological approaches for the treatment of presbyopia have been introduced to the marketplace or are in the developmental pipeline. The approaches vary in invasiveness, duration of effect, reversibility, risk/benefit ratio, and clinical results. The advantages and disadvantages for each are discussed. Corneal surgical interventions aim to provide improved near and intermediate vision in patients with presbyopia through refractive means that extend ocular depth of focus through shape modification. The use of miotic drops or corneal lamellar implants extend depth of focus with the "pinhole" aperture size reduction effect. Unlike in adults younger than 40 years, the refractive status of the patient with presbyopia is not stable. Hence, procedures that provide a permanent refractive change may not provide long-term full correction; eye drops or other treatments that are self-reversing in time or are easily reversible may be used as needed. On the horizon, procedures are being explored that may add years of functional lens accommodation by preserving the deformable gel properties of the lens. [J Refract Surg. 2021;37(6 Suppl):S20-S27.].

SIGNIFICANCE/CONCLUSIONS: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. PURPOSE/OBJECTIVE: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. METHODS: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. RESULTS: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. CONCLUSIONS: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.

Purpose/UNASSIGNED:Phentolamine mesylate ophthalmic solution (PMOS), applied to the eye topically, was shown previously to have beneficial effects in patients with dim light vision disturbances (DLD), including decreased pupil diameter (PD), improved best-corrected distance visual acuity (BCDVA), as well as lower intraocular pressure (IOP). The ORION-1 trial evaluated the long-term safety and efficacy of PMOS in a glaucomatous, presbyopic population. Patients and Methods/UNASSIGNED:In this randomized, double-masked, multi-center, placebo-controlled, multiple-dose Phase 2b trial, 39 patients with elevated IOP were randomized to receive one evening dose of study medication or placebo for 14 days. The primary outcome measure was mean change in diurnal IOP, and the key secondary outcome measures included changes in PD, distance-corrected near visual acuity (DCNVA), and conjunctival hyperemia. Results/UNASSIGNED:= 0.0163), with a trend for 2- and 3-line improvements at all time points. There was no statistical difference in conjunctival hyperemia compared to placebo. Conclusion/UNASSIGNED:Although mean IOP was not lowered significantly, daily evening dosing of 1% PMOS was found to be well tolerated with no daytime conjunctival redness and demonstrated improvement in DCNVA with sustained PD reduction in a glaucomatous and presbyopic population. Smaller pupil size can have beneficial effects in improving symptoms of presbyopia and DLD, which will be the focus of further studies.

Purpose : Phentolamine mesylate ophthalmic solution (PM) was previously shown to have short term beneficial effects in the eye (> 2 hours), including intra ocular pressure (IOP) lowering, pupil diameter (PD) decrease, and increase of visual acuity and contrast sensitivity, while causing mild to moderate conjunctival hyperemia. This study evaluates the chronic safety and efficacy of 1% PM once-a-day evening dose in the presbyopic population. Methods : In this randomized, double-masked, placebo-controlled, multiple dose Phase 2b study in 39 subjects (mean age = 60 yrs, IOP > 22 and <30 mmHg), we evaluated the dosing regimen, safety, vision performance and IOP efficacy following once daily evening 1% PM dosing for 14 days. The key endpoints were the mean change in diurnal IOP, PD, distance corrected near visual acuity (DCNVA) and conjunctival hyperemia at day 8 and 15. Analysis of covariates (ANCOVA) was performed to assess statistical significance between treatment groups for each parameter. Results : 1% PM in the evening led to a-2.30 mmHg day 15 mean diurnal IOP change from baseline compared to a-2.18 mmHg change for placebo (p=0.894). There was a trend toward greater IOP lowering in subjects with lower IOP baselines (-3.57 mmHg for PM compared to +3.10 mmHg for placebo, p=0.0489, at baseline IOP < 22 mmHg). PM led to-20.2% and-20.0% mean change in PD at Day 8 and Day 15 compared to-1.5% and +1.9% for placebo in photopic conditions (p<0.0001), with similar results in mesopic conditions. PD reduction for PM was sustained through 36 hours post-dose at Day 16 (-20.6% compared to +6.0%, p<0.0001). Further, more patients with PM showed at least 1 line of improvement in DCNVA at Day 15 (63.2% compared to 20.0%, p=0.0259), with a trend for 2-and 3-lines at all days. There was no conjunctival hyperemia difference between the two groups at 8am on day 15 (p=0.3476), no burning, ptosis, tachyphylaxis, rebound or other AEs/SAEs. Conclusions : 1% PM is well tolerated in the eye and the evening dose regimen minimizes eye redness during daytime while benefiting near visual acuity in the presbyopic population. The sustained (36 hour) pupil modulation and visual acuity effect data suggest that PM is a good candidate for remediating photic phenomena and night vision disturbances (NVD). Follow up clinical trials shall investigate the effect of 1% PM in patients with NVD

Graphical abstract key: ADHD, attention deficit hyperactivity disorder; ASD, atrial septal defect; DD, developmental delay; EEG, electroencephalogram; Ht, height; ID, intellectual disability; OCD, obsessive-compulsive disorder; OFC, open fontanelle; PDA, patent ductus arteriosis; PFO, patent foramen ovale; VSD, ventricular septal defect; Wt, weight.