Variants in myelin regulatory factor (MYRF) cause autosomal dominant and syndromic nanophthalmos in humans and retinal degeneration in mice.

Nanophthalmos is a rare, potentially devastating eye condition characterized by small eyes with relatively normal anatomy, a high hyperopic refractive error, and frequent association with angle closure glaucoma and vision loss. The condition constitutes the extreme of hyperopia or farsightedness, a common refractive error that is associated with strabismus and amblyopia in children. NNO1 was the first mapped nanophthalmos locus. We used combined pooled exome sequencing and strong linkage data in the large family used to map this locus to identify a canonical splice site alteration upstream of the last exon of the gene encoding myelin regulatory factor (MYRF c.3376-1G>A), a membrane bound transcription factor that undergoes autoproteolytic cleavage for nuclear localization. This variant produced a stable RNA transcript, leading to a frameshift mutation p.Gly1126Valfs*31 in the C-terminus of the protein. In addition, we identified an early truncating MYRF frameshift mutation, c.769dupC (p.S264QfsX74), in a patient with extreme axial hyperopia and syndromic features. Myrf conditional knockout mice (CKO) developed depigmentation of the retinal pigment epithelium (RPE) and retinal degeneration supporting a role of this gene in retinal and RPE development. Furthermore, we demonstrated the reduced expression of Tmem98, another known nanophthalmos gene, in Myrf CKO mice, and the physical interaction of MYRF with TMEM98. Our study establishes MYRF as a nanophthalmos gene and uncovers a new pathway for eye growth and development.

The Evolution of the American Board of Ophthalmology Written Qualifying Examination.

Since the inception of board certification in ophthalmology in 1916, a written assessment of candidates' knowledge base has been an integral part of the certification process. Although the committee structure and technique for writing examination questions has evolved over the past 100 years, the written qualifying examination remains an essential tool for assessing the competency of physicians entering the workforce. To develop a fair and valid examination, the American Board of Ophthalmology builds examination questions using evidence-based, peer-reviewed literature and adheres to accepted psychometric assessment standards.

Long-term efficacy of the Baerveldt 250 mm2 compared with the Baerveldt 350 mm2 implant.

PURPOSE: To investigate the long-term surgical outcomes of the Baerveldt 250 mm2 versus Baerveldt 350 mm2 glaucoma drainage implants (GDIs) (Abbott Laboratories Inc., Abbott Park, IL) in the treatment of refractory glaucoma. DESIGN: Comparative case study. PARTICIPANTS: A total of 89 consecutive eyes in 86 patients treated at Dean McGee Eye Institute between January 2006 and December 2008. METHODS: We retrospectively reviewed patient data from the following postoperative visits: 1 week, 1 month, 2 months, 3 months, 6 months, and every 3 months thereafter. Postoperative complications were also recorded. The mean follow-up time was 40 months (range, 2-78 months) for the Baerveldt 250 mm2 group and 31 months (range, 3-75 months) for the Baerveldt 350 mm2 group. MAIN OUTCOME MEASURES: The primary outcome measure was surgical success. Secondary outcome measures included visual acuity (VA), intraocular pressure (IOP), and number of medications. RESULTS: There was no difference in surgical success (P=0.98). No significant differences were observed in VA measured using the logarithm of the minimum angle of resolution (logMAR) scale, IOP, and number of medications at the last visit (P=0.09, 0.23, and 0.82, respectively). Complication and failure rates were comparable (P=0.82 and 0.64, respectively). CONCLUSIONS: With a mean follow-up of 40 and 31 months, no differences in surgical success, VA, IOP, number of medications at the last visit, and complication/failure rates were noted between the Baerveldt 250 mm2 and 350 mm2 GDIs, respectively. The size of the GDI may not be associated with surgical outcomes.

An IRIS Registry-Based Assessment of Primary Open-Angle Glaucoma Practice Patterns in Academic Versus Nonacademic Settings.

PURPOSE: To compare patient demographic data; level of severity; and clinical, diagnostic, and surgical practice patterns in patients with primary open-angle glaucoma (POAG) in an academic setting vs nonacademic setting using the American Academy of Ophthalmology IRIS Registry (Intelligent Research in Sight). METHODS: A retrospective cohort study of IRIS Registry data that included patients with POAG who were seen between January 2016 and December 2019 and had at least 1 year of follow-up. RESULTS: Of 3 707 084 distinct eyes with POAG, 3% (109 920) were included in the academic subcohort and 97% (3 597 164) were included in the nonacademic subcohort. Among the findings of greatest note (P < .0001 for all comparisons) were a higher proportion of eyes of Black patients, a higher proportion of eyes with level 3 severity, and a higher mean cup-to-disc ratio in eyes in the academic setting. The relative frequency of gonioscopy, pachymetry, and visual field testing in conjunction with new patient visits was also notably higher in the academic setting. For glaucoma surgical procedures, the greatest proportional differences in relative frequency were seen for tube shunt procedures (2.55-fold higher in the academic setting), iStent and Hydrus procedures (2.52-fold higher in the nonacademic setting), and endoscopic cyclophotocoagulation (5.80-fold higher in the nonacademic setting). CONCLUSIONS: Based on IRIS Registry data, notable differences appear to exist with regard to ethnoracial groups, glaucoma severity, and diagnostic and surgical practice patterns in academic vs nonacademic settings. By understanding these differences, potential opportunities exist in the development of educational programs related to clinical and surgical glaucoma care.

The clinical impact and incidence of periocular pigmentation associated with either latanoprost or bimatoprost therapy.

PURPOSE: To evaluate the incidence and characteristics of periocular pigmentation with latanoprost versus bimatoprost. METHODS: A retrospective, active-controlled comparison of consecutive patients treated with latanoprost or bimatoprost for 12 months evaluating patients to determine the incidence, characteristics, and reversibility of periocular pigmentation. RESULTS: Periocular pigmentation was found in 1% patients treated with latanoprost and 6% patients treated with bimatoprost within 12 months of beginning treatment (p = 0.004). CONCLUSIONS: This study suggests that periocular pigmentation may develop after treatment with latanoprost or bimatoprost.

Laser bleb reduction for bleb dissection with krypton green laser: technique and outcomes.

PURPOSE: Lasers have been used to treat dysfunctional blebs, but the laser remodeling of blebs that dissect into the palpebral fissure has not been reported. We describe the unique use of krypton green laser to treat dissected blebs and discuss treatment outcomes. PATIENTS AND METHODS: Retrospective review of consecutive patients undergoing laser bleb reductions (LBRs) over a 6-year period. Failure was defined as persistent dissection and/or symptoms or loss of intraocular pressure (IOP) control despite medications. RESULTS: Sixteen patients underwent a total of 23 LBRs and were followed-up for a mean of 12.4 months (median = 9.5 mo). Ten patients (63%) were treated successfully, and 6 patients (37%) failed treatment. Persistent dissection and/or symptoms were the most common reasons for failure (5/6), whereas 1 patient lost IOP control. Three (30%) of those treated successfully required the reintroduction of ocular hypotensive medications for pressure control. The mean IOP increased from 9.1 +/- 5.2 mm Hg before treatment to 11.7 +/- 8.1 mm Hg after treatment (P = 0.02). Common complications included intraoperative discomfort (26%), conjunctival injection (22%), postoperative discomfort (13%), and dissection into the untreated side (9%). In the failure group, more laser spots (P = 0.05) and higher power levels (P = 0.00001) were used. CONCLUSIONS: Krypton LBR may be a useful initial treatment modality for symptomatic bleb dissection. Success rates may be modest, but most adverse effects are mild and/or transient; however, significant loss of IOP control can occasionally occur.

Comparison of Outcomes of Laser Trabeculoplasty Performed by Optometrists vs Ophthalmologists in Oklahoma.

IMPORTANCE: Oklahoma is one of the few states where optometrists have surgical privileges to perform laser trabeculoplasty (LTP). Optometrists in other states are lobbying to obtain privileges to perform LTP and other laser procedures. Little is known whether outcomes of patients undergoing this procedure by optometrists are similar to those undergoing LTP by ophthalmologists. OBJECTIVE: To compare outcomes of LTPs performed by ophthalmologists with those performed by optometrists to determine whether differences exist in the need for additional LTPs. DESIGN, SETTING, AND PARTICIPANTS: This retrospective longitudinal cohort study used a health care claims database containing more than 1000 eyes of Medicare enrollees with glaucoma who underwent LTP in Oklahoma from January 1, 2008, through December 31, 2013. For each procedure, the data specify the type of eye care professional who performed the LTP. The rate of LTPs performed by ophthalmologists that required 1 or more additional LTPs in the same eye was compared with the rate of LTPs performed by optometrists. Regression models determined factors affecting risk of undergoing more than 1 LTP in the same eye. MAIN OUTCOMES AND MEASURES: Proportion of enrollees requiring additional LTPs, hazard ratio with 95% CIs of undergoing additional LTPs. RESULTS: A total of 1384 eyes of 891 eligible patients underwent LTP from January 1, 2008, through December 31, 2013. There were 1150 eyes that received LTP (83.1%) by an ophthalmologist and 234 eyes (16.9%) that had the procedure performed by an optometrist. The mean (SD) age at the initial LTP was 77.7 (7.5) years for enrollees with ophthalmologist-performed LTP and 77.6 (8.0) years for those with optometrist-performed LTP (P = .89). Among the 1384 eyes receiving LTP, 258 (18.6%) underwent more than 1 LTP in the same eye. The proportion of eyes undergoing LTP by an optometrist requiring 1 or more subsequent LTP session (35.9%) was more than double the proportion of eyes that received this procedure by an ophthalmologist (15.1%). Medicare beneficiaries undergoing LTP by optometrists had a 189% increased hazard of requiring additional LTPs in the same eye compared with those receiving LTP by ophthalmologists (hazard ratio, 2.89; 95% CI, 2.00-4.17; P < .001) after adjusting for potential confounders. CONCLUSIONS AND RELEVANCE: Considerable differences exist among the proportions of patients requiring additional LTPs comparing those who were initially treated by ophthalmologists with those initially treated by optometrists. Health policy makers should be cautious about approving laser privileges for optometrists practicing in other states until the reasons for these differences are better understood.

Intermediate term safety and efficacy of transscleral cyclophotocoagulation after tube shunt failure.

PURPOSE: To determine the efficacy and safety of diode transscleral cyclophotocoagulation (TSCPC) after tube shunt failure. PATIENTS AND METHODS: The patient population consisted of 32 eyes of 31 patients with uncontrolled glaucoma. Each eye had a previously implanted aqueous tube shunt and was currently on maximally tolerated medication. Each eye also underwent TSCPC treatment using the Iridex (Mountain View, CA) diode laser with a maximum of 360 degrees of treatment. All 31 charts were reviewed for data pertaining to demographics, treatment, ocular history, and follow-up clinical examinations. Safety was evaluated by complication data. Efficacy was evaluated in terms of TSCPC treatment parameters (number of laser applications, laser power, application duration, and degrees of ciliary body treated), intraocular pressure, number of hypotensive medications, and any further treatment required. RESULTS: With a mean (SD) follow-up of 17.1 (16.3) (median=11.7) months from the last treatment, the mean intraocular pressure decreased from 28.6 (10.2) mm Hg to 16.8 (7.5) mm Hg (35% reduction) at 3 months (n=30, P<0.0001) and to 14.7 (7.9) mm Hg (43% reduction) at 1 year (n=13, P<0.0001). Complications included hypotony (n=4), hyphema (n=2), failed corneal transplant (n=1), and loss of light perception (n=5). CONCLUSIONS: TSCPC has a significant ocular hypotensive effect on glaucoma refractory to both tube shunt and medical therapy. The safety of this intervention remains unclear in this high risk patient population and warrants further study.