Characteristics and Surgical Outcomes of Comitant Esotropia in an Adult Population Between 18 and 60 Years Old.

PURPOSE: To describe the clinical characteristics and surgical outcomes of adults with comitant non-accommodative esotropia. DESIGN: Retrospective case series METHODS: Retrospective review of medical records of patients 18 to 60 years old with comitant esotropia who underwent strabismus surgery at a tertiary eye care center between 2014 and 2023. The etiology of esotropia was categorized into three groups based on the disparity between near-distance angles of deviation: 1. basic esotropia (ETBA); 2. esotropia divergence insufficiency pattern (ETDI); or 3. esotropia convergence excess pattern (ETCE). The main outcome measures were strabismus characteristics and motor and sensory surgical outcomes. Surgical motor success was defined as a deviation that measured ≤ 10 prism diopters (PD). RESULTS: Of the 219 that met the inclusion criteria, most patients were female (140, 64%) and had a mean age of 36.7 ± 12.3 years (range 18-60 years). The majority were myopic (157, 72%) and reported diplopia (176/219, 80.3%). The ETCE group had the largest mean deviations at both distance (45.5 ± 11.5 PD) and near (64 ± 12.3 PD) while the ETBA group had the largest ranges at distance (31 ± 13.5 PD, range 3-90) and near (30 ± 15 PD, range 2- 85). Bilateral medial rectus recession (BMR) and unilateral recess-resect (R&R) procedures were performed with equal frequency (both 48%). Motor and sensory success were achieved more often with R&R than BMR, although only motor success was statistically significant (87.8% vs. 73.2%, p=0.0375 and 93.3% vs. 85.5%, p=0. 15 respectively). At the last encounter, 88.1% (119/135) of patients with pre-operative diplopia achieved single binocular vision. CONCLUSIONS: Regardless of the pattern of esotropia, strabismus surgery in adults with comitant non-accommodative esotropia resulted in good motor and sensory outcomes.

Analysis of Socioeconomic Factors Affecting Follow-Up in a Glaucoma Screening Program.

PURPOSE: To determine what socioeconomic factors affect follow-up in a glaucoma screening program. PATIENTS AND METHODS: This was a retrospective cohort study of six health fairs in South Florida from October 2012 to March 2013 among socially and economically disadvantaged populations. Visual acuity (VA), intraocular pressure (IOP), cup-to-disc ratio (CDR), and visual field testing were obtained to identify glaucoma suspects. Glaucoma suspects were defined as having intraocular pressure ≥24 mm Hg, cup-to-disc ratio of ≥0.6 in either eye, or glaucomatous defects on visual field testing. In July 2015, telephone surveys were administered to assess follow up and socioeconomic factors. RESULTS: Seventy-two out of 144 (50%) glaucoma suspects responded to the survey and were included in the analysis. Of the 72 respondents, average age was 52.8 years old and 65% were female. The most common race was African American (69%) and ethnicity was Haitian (51%). Glaucoma suspects who followed up were significantly more likely to have health insurance compared to those who did not follow up (74% vs 43%, p = 0.014). No significant difference in follow-up based on age (p = 0.125), education (p = 0.151), gender (p = 0.48), or ethnicity (p = 0.707) was identified. Of the 30 respondents, who did not follow up, the most common reasons were "no insurance" (57%, 17/30) and "not worried" (33%, 10/30). CONCLUSION: Insurance was the main socioeconomic factor in determining whether glaucoma suspects followed up after community health screenings. Streamlining social services could increase clinical access of glaucoma suspects.

Initial results from a first-in-human gene therapy trial on X-linked retinitis pigmentosa caused by mutations in RPGR.

Retinal gene therapy has shown great promise in treating retinitis pigmentosa (RP), a primary photoreceptor degeneration that leads to severe sight loss in young people. In the present study, we report the first-in-human phase 1/2, dose-escalation clinical trial for X-linked RP caused by mutations in the RP GTPase regulator (RPGR) gene in 18 patients over up to 6 months of follow-up (https://clinicaltrials.gov/: NCT03116113). The primary outcome of the study was safety, and secondary outcomes included visual acuity, microperimetry and central retinal thickness. Apart from steroid-responsive subretinal inflammation in patients at the higher doses, there were no notable safety concerns after subretinal delivery of an adeno-associated viral vector encoding codon-optimized human RPGR (AAV8-coRPGR), meeting the pre-specified primary endpoint. Visual field improvements beginning at 1 month and maintained to the last point of follow-up were observed in six patients.

Choroideremia Gene Therapy Phase 2 Clinical Trial: 24-Month Results.

PURPOSE: To report the final results of a phase 2 high-dose gene therapy clinical trial in choroideremia. METHODS: Design: Phase 2 clinical trial. PARTICIPANTS: Six men (aged 32-72 years) with genetically-confirmed advanced choroideremia. Patients received subfoveal injection of AAV2-REP1 (1011 genome particles in 0.1 mL) in the worse-sighted eye. OUTCOME MEASURES: Primary measure was best-corrected visual acuity (BCVA) change from baseline in the treated eye compared to the untreated eye. Secondary endpoints included change from baseline in microperimetry, fundus autofluorescence, and spectral-domain optical coherence tomography (OCT). Safety evaluations included adverse events, viral shedding in body fluids, and vector antibody responses. RESULTS: Baseline mean ETDRS BCVA was 65.3 ± 8.8 (SD, range 56-77, 20/32-20/80) letters in the treated eyes and 77.0 ± 4.2 (69-81, 20/25-20/40) letters in the untreated eyes. At 2 years, 1 treated eye improved by 10 letters and another by 5 letters, while 1 untreated eye improved by 4 letters. All other eyes were within 2 letters of baseline. Baseline microperimetry sensitivities in the treated eyes were poor (1.2 ± 2.1 (0, 5.1) dB) and showed no significant change. No serious adverse event occurred. Two patients developed an atrophic retinal hole in a nonfunctioning macular area where baseline OCT showed preexisting thinning. Intraoperative microscope-integrated OCT allowed proper subretinal injection with avoidance of excessive foveal stretching and macular hole formation. CONCLUSIONS: Sustained improvement or maintenance of BCVA is achievable in choroideremia with high-dose AAV2-REP1, indicating BCVA is a viable primary outcome in advanced choroideremia. Choroideremia gene therapy delivered with intraoperative OCT has a good safety profile.

Macular Retinal Sublayer Thicknesses in G11778A Leber Hereditary Optic Neuropathy.

BACKGROUND AND OBJECTIVE: To determine macular retinal sublayer thickness changes in G11778A Leber hereditary optic neuropathy (LHON). PATIENTS AND METHODS: The authors performed a cross-sectional study by segmenting spectral-domain Cirrus OCT (Carl Zeiss Meditec, Dublin, CA) 512 × 128 macular cube scans from a prospective, observational study of G11778A LHON. The thickness of the retinal sublayers of LHON affected subjects and asymptomatic carriers were compared to those of a normal group. RESULTS: The study included 20 LHON-affected subjects (13 males; age: 31 years ± 14 years, range: 10 years to 61 years; time since onset of visual loss: 5.9 years ± 8.7 years; 0.4-29.8), 31 asymptomatic LHON carriers (five males; age: 38 years ± 18 years, range: 9 years to 65 years), and 14 normal subjects (five males; age: 39 years ± 13 years, range: 23 years to 61 years). The retinal sublayer thickness parameters were not significantly correlated with age in any of the groups. There were no differences between carriers and normal subjects for thickness of total retina or any sublayer. Affected LHON retinal nerve fiber layer (RNFL) and ganglion cell layer plus inner plexiform layer (GCL+IPL) were thinner, whereas the photoreceptor outer segment (OS) layer was thicker than carriers and normal subjects (P values ranged from .042 to < .001), except for the OS layer in the inferior inner ring and temporal outer ring. Differences between groups were not significant in the inner nuclear layer plus outer plexiform layer (INL+OPL). The affected LHON outer nuclear layer plus inner segment layer was thicker in some quadrants, and the affected LHON choroid layer was generally thinner than carriers and normal subjects; however, these differences were not significant after accounting for age. CONCLUSION: LHON-affected patients have thickened photoreceptor OS layers in spite of having thinner RNFL and GCL+IPL layers. The findings indicate LHON also has an effect on the morphology of the photoreceptors. [Ophthalmic Surg Lasers Imaging Retina. 2016;47:802-810.].

Choroidal Thickness in Eyes With Central Geographic Atrophy Secondary to Stargardt Disease and Age-Related Macular Degeneration.

BACKGROUND AND OBJECTIVE: Choroidal thickness (CT) measurements from eyes with similar areas of macular geographic atrophy (GA) secondary to age-related macular degeneration (AMD) and Stargardt disease (STGD) were compared to determine whether GA from different diseases had a similar or different effect on the underlying subfoveal choroid. PATIENTS AND METHODS: Eyes with the diagnosis of central GA secondary to STGD and AMD were matched, with subfoveal CT measurements obtained from the central B-scan using an enhanced depth imaging protocol. The area of GA was measured using fundus autofluorescence (FAF) imaging. AMD eyes were divided into those with and without reticular pseudodrusen. RESULTS: A total of 22 eyes of 22 patients were included in the STGD and AMD groups and were matched with respect to the area of GA. The mean age of the STGD patients was 48.9 years (standard deviation [SD]=17.1), and the mean age was 81.8 years (SD=6.2) for the AMD patients. Mean area measurements of GA for the STGD and AMD groups were 5.4 mm2 (SD=4.1) and 5.1 mm2 (SD=4.0), respectively (P=.83). After adjusting for age and axial length, eyes with STGD had a mean CT measurement greater than the AMD eyes (336.1 µm vs. 198.1 µm, respectively; P=.039). However, this difference was driven by AMD eyes with reticular pseudodrusen (RPD) and by a single Stargardt case with a very thick choroid. Eyes with RPD had statistically thinner subfoveal CT measurements when compared with all other groups. CONCLUSION: A small but statistically significant increase in the CT of STGD eyes was observed when compared with normal controls and AMD eyes without RPD. However, this small increase in CT was driven by a single case with a markedly thicker choroid within the STGD group, so it is unlikely that a clinically significant difference exists. However, AMD eyes with GA and RPD had significantly thinner subfoveal CT measurements.

Relationship Between Optic Nerve Protrusion Measured by OCT and MRI and Papilledema Severity.

PURPOSE: To develop measures of optic nerve protrusion length (NPL) from optical coherence tomography (OCT) and magnetic resonance imagining (MRI) and compare these measures with papilledema severity in idiopathic intracranial hypertension (IIH). METHODS: Optical coherence tomography and MRI scans were obtained from 11 newly diagnosed untreated IIH patients (30 ± 10 years; body mass index [BMI] 36 ± 4 kg/m2). Optic nerve protrusion length was measured for each eye using OCT and MRI independently. The relationship between the NPL measures and their association with the Frisen scale for papilledema severity were assessed. Two different OCT-based measures of NPL were derived to assess the influence of the retinal thickness on the association with papilledema severity. Additional OCT scans from 11 healthy subjects (38 ± 7 years) were analyzed to establish reliability of the NPL measurement. RESULTS: Optical coherence tomography and MRI measurements of NPL were significantly linearly correlated (R = 0.79, P < 0.0001). Measurements of NPL from OCT and MRI were significantly associated with Frisen papilledema grade (P < 0.0001). Mean OCT measurement of NPL in the papilledema cohort was significantly larger than in the healthy cohort (0.62 ± 0.24 vs. 0.09 ± 0.03 mm, P < 0.0001). CONCLUSIONS: Significant linear correlation between OCT and MRI measurements of NPL supports the reliability of the OCT-based measurements of NPL in papilledema. Significant association between the papilledema grade and OCT- and MRI-based measurements of NPL highlights the potential of NPL as an objective and more sensitive marker of papilledema severity than the Frisen scale.

Dilated eye examination screening guideline compliance among patients with diabetes without a diabetic retinopathy diagnosis: the role of geographic access.

OBJECTIVE: To estimate the prevalence of, and factors associated with, dilated eye examination guideline compliance among patients with diabetes mellitus (DM), but without diabetic retinopathy. RESEARCH DESIGN AND METHODS: Utilizing the computerized billing records database, we identified patients with International Classification of Diseases (ICD)-9 diagnoses of DM, but without any ocular diagnoses. The available medical records of patients in 2007-2008 were reviewed for demographic and ocular information, including visits through 2010 (n=200). Patients were considered guideline compliant if they returned at least every 15 months for screening. Participant street addresses were assigned latitude and longitude coordinates to assess their neighborhood socioeconomic status (using the 2000 US census data), distance to the screening facility, and public transportation access. Patients not compliant, based on the medical record review, were contacted by phone or mail and asked to complete a follow-up survey to determine if screening took place at other locations. RESULTS: The overall screening compliance rate was 31%. Patient sociodemographic characteristics, insurance status, and neighborhood socioeconomic measures were not significantly associated with compliance. However, in separate multivariable logistic regression models, those living eight or more miles from the screening facility were significantly less likely to be compliant relative to those living within eight miles (OR=0.36 (95% CI 0.14 to 0.86)), while public transit access quality was positively associated with screening compliance (1.34 (1.07 to 1.68)). CONCLUSIONS: Less than one-third of patients returned for diabetic retinopathy screening at least every 15 months, with transportation challenges associated with noncompliance. Our results suggest that reducing transportation barriers or utilizing community-based screening strategies may improve compliance.

Ventriculoperitoneal shunt as a treatment of visual loss in idiopathic intracranial hypertension.

BACKGROUND: The aims of this study were to evaluate visual function outcomes in idiopathic intracranial hypertension (IIH) patients who underwent ventriculoperitoneal (VP) shunt for visual loss and to determine a VP shunt survival curve over time. METHODS: A retrospective medical record review was performed of all new IIH patients first evaluated at our institution who underwent VP shunt placement over a 7-year period (2004-2010). There were 2 primary outcome measures: the first being visual acuity (VA) and the second being shunt survival. Patients who received VP shunt for visual loss were included in the visual outcome analysis, and all patients who received VP shunt for any reason were included in the shunt survival analysis. RESULTS: Of the 338 new patients with IIH, 19 patients (6%) met the inclusion criteria and 17 underwent VP shunt for visual loss and 2 for headaches. Average follow-up was 21.2 months (range, 5-1,342 days). Of the 17 patients who had VP shunt for visual loss, 5 patients had optic nerve sheath fenestration (ONSF) surgery before VP shunt, and 1 patient had bilateral ONSF surgery after VP shunt. Median VA before shunt was 20/200 in the worse eye (range, 20/20 to NLP) and 20/40 in the better eye (20/20 to HM). Median VA after shunt was 20/60 in the worse eye (20/20 to lumboperitoneal) and 20/30 in the better eye (20/20 to 20/800). The improvement in VA was statistically significant in both worse eyes (P = 0.002, Wilcoxon signed-rank test) and better eyes (P = 0.028). The mean automated visual field (AVF) mean deviation (MD) of available AVFs before shunt was 223.36 dB (range, 233.38 to 27.01 dB) for the worse eye (n = 11) and 219.66 dB (230.11 to 25.91 dB) for the better eye (n = 11). Mean AVF MD deviation of available AVFs after shunt was 220.68 dB (232.13 to 23.97 dB) for the worse eye (n = 11) and 216.35 dB (232.13 to 21.00 dB) for the better eye (n = 11): this improvement was not significant (P = 0.27, P = 0.26, respectively). Independent masked record reviews by 3 neuro-ophthalmologists showed that 9 (53%) patients improved, 5 (29%) unchanged, 1 (6%) worsened, and 2 (12%) were indeterminate. Kaplan-Meier analysis showed a persistent steady decrease of functioning VP shunts over the entire period of 36 months with 80%, 65%, and 48% of VP shunts functioning without replacement, removal, or revision at 12, 24, and 36 months, respectively. CONCLUSION: VP shunts improve or stabilize most IIH patients presenting with severe progressive visual loss or those with visual loss refractive to medical treatment and ONSF. Survival analysis shows persistent decrease of functioning shunts over time.

Trial end points and natural history in patients with G11778A Leber hereditary optic neuropathy : preparation for gene therapy clinical trial.

IMPORTANCE Establishing the natural history of G11778A Leber hereditary optic neuropathy (LHON) is important to determine the optimal end points to assess the safety and efficacy of a planned gene therapy trial. OBJECTIVE To use the results of the present natural history study of patients with G11778A LHON to plan a gene therapy clinical trial that will use allotopic expression by delivering a normal nuclear-encoded ND4 gene into the nuclei of retinal ganglion cells via an adeno-associated virus vector injected into the vitreous. DESIGN, SETTING, AND PARTICIPANTS A prospective observational study initiated in 2008 was conducted in primary and referral institutional practice settings. Participants included 44 individuals with G11778A LHON, recruited between September 2008 and March 2012, who were evaluated every 6 months and returned for 1 or more follow-up visits (6-36 months) as of August 2012. EXPOSURES Complete neuro-ophthalmic examination and main measures. MAIN OUTCOMES AND MEASURES Visual acuity, automated visual field testing, pattern electroretinogram, and spectral-domain optical coherence tomography. RESULTS Clinical measures were stable during the follow-up period, and visual acuity was as good as or better than the other visual factors used for monitoring patients. Based on a criterion of 15 or more letters from the Early Treatment Diabetic Retinopathy Study chart, 13 eyes of 8 patients (18%) improved, but 24 months after the onset of symptoms, any further improvements were to no better than 20/100. Acuity recovery occurred in some patients despite continued marked retinal nerve fiber layer thinning indistinguishable from that in patients who did not recover visual acuity. CONCLUSIONS AND RELEVANCE Spontaneous improvement of visual acuity in patients with G11778A LHON is not common and is partial and limited when it occurs, so improvements in vision with adeno-associated virus-mediated gene therapy of a synthetic wild-type ND4 subunit gene should be possible to detect with a reasonable sample size. Visual acuity appears to be the most suitable primary end point for the planned clinical trial.

Retinal ganglion cell dysfunction in asymptomatic G11778A: Leber hereditary optic neuropathy.

PURPOSE: To report the serial evaluation of asymptomatic eyes of subjects with mutated G11778A mitochondrial DNA. METHODS: Forty-five asymptomatic G11778A Leber hereditary optic neuropathy (LHON) carriers and two patients with the mutation who developed unilateral visual loss underwent testing that included visual acuity, automated visual field, pattern electroretinogram (PERG), and spectral-domain optical coherence tomography every 6 months between September 2008 and March 2012. RESULTS: Visual acuity, visual fields, and retinal nerve fiber layer thickness remained stable within the normal range. Mean PERG amplitudes of carriers dropped progressively by ∼ 40% from baseline to 36 months. In addition, comparisons with the fellow eyes of patients with unilateral optic neuritis revealed a 3.4 ETDRS (Early Treatment Diabetic Retinopathy Study) letter loss in the LHON carriers. A single carrier developed visual loss, with PERG amplitudes dropping by half. In one of two LHON cases who presented with unilateral visual loss, visual acuity in the asymptomatic eye was ∼ 20/40 at baseline. The PERG amplitude of this eye was reduced to ∼ 30% of normal. Six months later, his visual acuity had dropped to ∼ 20/500. A second patient who was ∼ 20/20 and had a visual field defect in the asymptomatic eye at baseline remained at this level for the 18 months of follow-up. His PERG amplitudes were similar to those of asymptomatic carriers, with 0.78 µV at baseline that did not decline with follow-up. CONCLUSIONS: Declines of the PERG amplitude suggest subclinical retinal ganglion cell dysfunction in asymptomatic G11778A subjects, which is progressive.

Differentiating mild papilledema and buried optic nerve head drusen using spectral domain optical coherence tomography.

PURPOSE: To evaluate the clinical utility of spectral domain optical coherence tomography (SD-OCT) in differentiating mild papilledema from buried optic nerve head drusen (ONHD). DESIGN: Comparative case series. PARTICIPANTS: Sixteen eyes of 9 patients with ultrasound-proven buried ONHD, 12 eyes of 6 patients with less than or equal to Frisén grade 2 papilledema owing to idiopathic intracranial hypertension. Two normal fellow eyes of patients with buried ONHD were included. METHODS: A raster scan of the optic nerve and analysis of the retinal nerve fiber layer (RNFL) thickness was performed on each eye using SD-OCT. Eight eyes underwent enhanced depth imaging SD-OCT. Images were assessed qualitatively and quantitatively to identify differentiating features between buried ONHD and papilledema. Five clinicians trained with a tutorial and masked to the underlying diagnosis independently reviewed the SD-OCT images of each eye to determine the diagnosis. MAIN OUTCOME MEASURES: Differences in RNFL thickness in each quadrant between the 2 groups and diagnostic accuracy of 5 independent clinicians based on the SD-OCT images alone. RESULTS: We found no difference in RNFL thickness between buried ONHD and papilledema in any of the 4 quadrants. Diagnostic accuracy among the readers was low and ranged from 50% to 64%. The kappa coefficient of agreement among the readers was 0.35 (95% confidence interval, 0.19-0.54). CONCLUSIONS: We found that SD-OCT is not clinically reliable in differentiating buried ONHD and mild papilledema.