Author: Ophthalmology

Mitochondrial Retinal Dystrophy Associated with the m.3243A>G Mutation – Corrected Proof

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Objective: To describe the spectrum of retinal abnormalities associated with the m.3243A>G mutation in the mitochondrial MTTL1 gene and to analyze putative correlations among the severity of retinal abnormalities, disease severity in other organ systems, and heteroplasmy levels.Design: Observational, cohort-based, cross-sectional study.Participants: Twenty-nine patients carrying the m.3243A>G mutation.Methods: Extensive clinical examinations, including visual acuity testing, indirect ophthalmoscopy, color fundus photography, fundus autofluorescence (FAF), high-resolution optical coherence tomography (OCT), and central visual field analysis. In selected patients, Goldmann perimetry, fluorescein angiography, full-field electroretinography (ERG) and electro-oculography (EOG), and color vision testing were performed. Heteroplasmy levels of the m.3243A>G mutation were measured in leukocytes, urinary epithelial cells (UECs), and buccal mucosa. The Newcastle Mitochondrial Disease Adult Scale (NMDAS) score was measured for all patients.Main Outcome Measures: Age at onset, visual acuity, fundus appearance, FAF, OCT findings, systemic disease features, heteroplasmy levels, and NMDAS scores.Results: Twenty-five of the 29 mutation carriers (86%) had retinal abnormalities that could be classified into 4 grades. Six patients (21%) had grade 1 retinal dystrophy with fine pigment abnormalities that were clearly visible with FAF and fluorescein angiography. Eleven patients (38%) had grade 2 abnormalities that were characterized by yellowish or mildly pigmented deposits in the early stage; in advanced grade 2, these pigment changes encompassed the entire macula and often encircled the optic disc. Six patients (21%) had grade 3 disease in which profound chorioretinal atrophy was present outside the fovea. Two patients (7%) with retinal abnormalities had grade 4 disease, in which the fovea was affected by atrophy, with marked loss of visual acuity. The grade of mitochondrial retinal dystrophy correlated significantly with both age (r = −0.483, P = 0.008) and visual acuity (r = −0.614, P  G mutation has specific characteristics that can be classified into 4 grades based on the findings on ophthalmoscopy, FAF, and OCT. However, because the maternal inheritance pattern can be masked and the systemic disease associations can be variable or even absent, the disease may be misdiagnosed.Financial Disclosure(s): Proprietary or commercial disclosure may be found after the references.

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Ophthalmic Surgery Simulator Training Improves Resident Performance of Capsulorhexis in the Operating Room – Corrected Proof

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Purpose: To assess the effect of a Capsulorhexis Intensive Training Curriculum (CITC) on the rates of errant, continuous, curvilinear capsulorhexes (CCCs) during cataract surgery among resident surgeons at a teaching hospital.Design: Retrospective educational interventional case series.Participants and Controls: A total of 1037 consecutive cataract surgeries performed at Harbor-UCLA Medical Center during 4 consecutive academic years were considered. The baseline cohort consists of 434 cataract surgeries performed during the 2 academic years before the intervention. The postintervention cohort consists of 603 cataract surgeries performed during the following 2 consecutive academic years.Intervention: The principal intervention was the introduction of the CITC for residents on the Eyesi (VRmagic, Mannheim, Germany) ophthalmic virtual reality surgical simulator.Main Outcome Measures: The main outcome measure was the rate of errant CCCs among the capsulorhexes performed during resident surgical cases. Errant CCCs were defined as attempted CCCs that resulted in the attending physician taking over, radialization of the CCC, conversion to can-opener capsulorhexis, or any combination of the 3 aforementioned conditions. Secondary measures included the use of trypan blue during CCC and correlating errant CCC and surgeons’ level of training (postgraduate year [PGY]).Results: There were 68 errant CCCs (15.7%) in the baseline cohort and 30 errant CCCs (5.0%; P < 0.0001) in the postintervention cohort, a 3.2-fold or 68% reduction. The use of trypan blue increased from 55.3% in the baseline cohort to 76.0% in the postintervention cohort (P < 0.00001), but within each cohort there was no significant difference in the rate of errant CCCs whether trypan blue was used or not. In the baseline cohort, there was a statistical trend toward fewer errant CCCs among PGY 4 (14.6%) compared with PGY 3 (22.8%) surgeons (P = 0.12). The postintervention cohort showed no significant difference in errant CCC rates between PGY 3 (4.4%) and PGY 4 (5.1%) surgeons (P = 1.00).Conclusions: This study strongly suggests that virtual reality surgical simulation training with the CITC on the Eyesi reduces the rate of errant capsulorhexes. The incorporation of a formal program for surgical training via virtual reality simulation should be strongly considered in ophthalmology resident surgical education to reduce the unnecessary risk of complications for live patients.Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

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The Ahmed Versus Baerveldt Study: Three-Year Treatment Outcomes – Corrected Proof

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Objective: To compare 2 commonly used aqueous drainage devices for the treatment of refractory glaucoma.Design: International, multicenter, randomized trial.Participants: Patients aged 18 years or older with uncontrolled or high-risk glaucoma refractory to maximum medical therapy, many of whom had failed trabeculoplasty and trabeculectomy.Methods: Eligible patients were randomized to an Ahmed-FP7 valve implant (New World Medical, Inc., Rancho Cucamonga, CA) or a Baerveldt-350 implant (Abbott Medical Optics, Inc., Santa Ana, CA) using a standardized surgical technique.Main Outcome Measures: The primary outcome was failure, defined as intraocular pressure (IOP) outside of the target range (5–18 mmHg, with ≥20% reduction from baseline) for 2 consecutive visits after 3 months, vision-threatening complications, de novo glaucoma procedures, or loss of light perception. Secondary outcome measures include IOP, medication use, visual acuity, complications, and interventions.Results: A total of 238 patients were enrolled and randomized; 124 received the Ahmed implant and 114 received the Baerveldt implant. Baseline characteristics were similar in both groups. Half the study group had secondary glaucoma, and 37% had previously failed trabeculectomy. The mean preoperative IOP was 31.4±10.8 mmHg on 3.1±1.0 glaucoma medications. Median baseline Snellen visual acuity was 20/100. At 3 years, the cumulative probability of failure was 51% in the Ahmed group and 34% in the Baerveldt group (P = 0.03). Mean IOP was 15.7±4.8 mmHg in the Ahmed group (49% reduction) and 14.4±5.1 mmHg in the Baerveldt group (55% reduction; P = 0.09). Mean number of glaucoma medications was 1.8±1.4 in the Ahmed group (42% reduction) and 1.1±1.3 in the Baerveldt group (65% reduction; P = 0.002). There was a moderate but similar decrease in visual acuity in both groups (P < 0.001). The 2 groups had similar complication rates (52% Ahmed, 62% Baerveldt; P = 0.12); however, the Baerveldt group had a higher rate of hypotony-related vision-threatening complications (0% Ahmed, 6% Baerveldt; P = 0.005). More interventions were required in the Baerveldt group, although the difference did not reach statistical significance (38% Ahmed, 50% Baerveldt; P = 0.07). Most complications were transient, and most interventions were slit-lamp procedures.Conclusions: Both devices were effective in reducing IOP and glaucoma medications. The Baerveldt group had a lower failure rate and required fewer medications than the Ahmed group after 3 years, but it experienced more hypotony-related vision-threatening complications.Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

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Peripheral Lesions Identified by Mydriatic Ultrawide Field Imaging: Distribution and Potential Impact on Diabetic Retinopathy Severity – Corrected Proof

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Objective: To assess diabetic retinopathy (DR) as determined by lesions identified using mydriatic ultrawide field imaging (DiSLO200; Optos plc, Scotland, UK) compared with Early Treatment Diabetic Retinopathy Study (ETDRS) 7-standard field film photography.Design: Prospective comparative study of DiSLO200, ETDRS 7-standard field film photographs, and dilated fundus examination (DFE).Participants: A total of 206 eyes of 103 diabetic patients selected to represent all levels of DR.Methods: Subjects had DiSLO200, ETDRS 7-standard field film photographs, and DFE. Images were graded for severity and distribution of DR lesions. Discrepancies were adjudicated, and images were compared side by side.Main Outcome Measures: Distribution of hemorrhage and/or microaneurysm (H/Ma), venous beading (VB), intraretinal microvascular abnormality (IRMA), and new vessels elsewhere (NVE). Kappa (κ) and weighted κ statistics for agreement.Results: The distribution of DR severity by ETDRS 7-standard field film photographs was no DR 12.5%; nonproliferative DR mild 22.5%, moderate 30%, and severe/very severe 8%; and proliferative DR 27%. Diabetic retinopathy severity between DiSLO200 and ETDRS film photographs matched in 80% of eyes (weighted κ = 0.74,κ = 0.84) and was within 1 level in 94.5% of eyes. DiSLO200 and DFE matched in 58.8% of eyes (weighted κ = 0.69,κ = 0.47) and were within 1 level in 91.2% of eyes. Forty eyes (20%) had DR severity discrepancies between DiSLO200 and ETDRS film photographs. The retinal lesions causing discrepancies were H/Ma 52%, IRMA 26%, NVE 17%, and VB 4%. Approximately one-third of H/Ma, IRMA, and NVE were predominantly outside ETDRS fields. Lesions identified on DiSLO200 but not ETDRS film photographs suggested a more severe DR level in 10% of eyes. Distribution in the temporal, superotemporal, inferotemporal, superonasal, and inferonasal fields was 77%, 72%, 61%, 65%, and 59% for H/Ma, respectively (P < 0.0001); 22%, 24%, 21%, 28%, and 22% for VB, respectively (P = 0.009); 52%, 40%, 29%, 47%, and 36% for IRMA, respectively (P < 0.0001), and 8%, 4%, 4%, 8%, and 5% for NVE, respectively (P = 0.03). All lesions were more frequent in the temporal fields compared with the nasal fields (P < 0.0001).Conclusions: DiSLO200 images had substantial agreement with ETDRS film photographs and DFE in determining DR severity. On the basis of DiSLO200 images, significant nonuniform distribution of DR lesions was evident across the retina. The additional peripheral lesions identified by DiSLO200 in this cohort suggested a more severe assessment of DR in 10% of eyes than was suggested by the lesions within the ETDRS fields. However, the implications of peripheral lesions on DR progression within a specific ETDRS severity level over time are unknown and need to be evaluated prospectively.Financial Disclosure(s): Proprietary or commercial disclosure may be found after the references.

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Assessment of Circumferential Angle-Closure by the Iris–Trabecular Contact Index with Swept-Source Optical Coherence Tomography – Corrected Proof

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Purpose: To evaluate the diagnostic performance of the iris–trabecular contact (ITC) index, a measure of the degree of angle-closure, using swept-source optical coherence tomography (SSOCT, CASIA SS-1000, Tomey Corporation, Nagoya, Japan) in comparison with gonioscopy.Design: Prospective observational study.Participants: A total of 108 normal subjects and 32 subjects with angle-closure.Methods: The SSOCT 3-dimensional angle scans, which obtain radial scans for the entire circumference of the angle, were performed under dark conditions and analyzed using customized software by a single examiner masked to the subjects’ clinical details. The ITC index was calculated as a percentage of the angle that was closed on SSOCT images. First-order agreement coefficient (AC1) statistics and area under the receiver operating characteristic curve (AUC) analyses were performed for angle-closure on the basis of the ITC index in comparison with gonioscopy.Main Outcome Measures: Angle-closure on gonioscopy was defined as nonvisibility of posterior trabecular meshwork for at least 2 quadrants. Agreement of the ITC index with gonioscopically defined angle-closure was assessed using the AC1 statistic.Results: Study subjects were predominantly Chinese (95.7%) and female (70.7%), with a mean age of 59.2 (standard deviation, 8.9) years. The median ITC index was 15.24% for gonioscopically open-angle eyes (n = 108) and 48.5% for closed-angle eyes (n = 32) (P = 0.0001). The agreement for angle-closure based on ITC index cutoffs (>35% and ≥50%) and gonioscopic angle-closure was 0.699 and 0.718, respectively. The AUC for angle-closure detection using the ITC index was 0.83 (95% confidence interval, 0.76–0.89), with an ITC index >35% having a sensitivity of 71.9% and specificity of 84.3%.Conclusions: The ITC index is a summary measure of the circumferential extent of angle-closure as imaged with SSOCT. The index had moderate agreement and good diagnostic performance for angle-closure with gonioscopy as the reference standard.Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

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One-Year Outcomes from a Prospective, Randomized, Eye-to-Eye Comparison of Wavefront-Guided and Wavefront-Optimized LASIK in Myopes – Corrected Proof

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Objective: To compare wavefront (WF)-guided and WF-optimized LASIK in myopes.Design: Prospective, randomized, eye-to-eye study.Participants: A total of 72 eyes of 36 participants with myopia with or without astigmatism.Methods: Participants were randomized to receive WF-guided or WF-optimized LASIK with the WaveLight Allegretto Eye-Q 400-Hz excimer laser platform (Alcon, Inc., Hüenberg, Switzerland). LASIK flaps were created using the 150-kHz IntraLase iFS (Abbott Medical Optics, Santa Ana, CA). Evaluations included measurement of uncorrected distance visual acuity (UDVA), corrected distance visual acuity (CDVA), <5% and <25% contrast sensitivity, and WF aberrometry. Patients also completed a validated questionnaire detailing symptoms on a quantitative scale.Main Outcome Measures: Safety, efficacy, predictability, refractive error, UDVA, CDVA, contrast sensitivity, and higher-order aberrations (HOAs).Results: The frequency with which the WF-guided and WF-optimized groups achieved postoperative UDVA of ≥20/16 or ≥20/20 and the frequency with which the groups lost 1 or 2 or more lines or maintained their preoperative CDVA were not statistically different from each other (all P > 0.05). The frequency with which the WF-guided group attained a refractive error within ±0.25 diopters of emmetropia was higher than in the WF-optimized group (67.6%, 95% confidence interval [CI], 50.4–84.8 vs. 41.2%, 95% CI, 23.2–59.2; P = 0.03). The WF-guided group’s mean UDVA was better than the WF-optimized group’s UDVA by approximately 1 Early Treatment Diabetic Retinopathy Study line (−0.17±0.11 logarithm of the minimum angle of resolution [logMAR], slightly <20/12 Snellen vs. −0.13±0.12, slightly >20/16; P = 0.05). There were no statistically significant differences in contrast sensitivity, astigmatism, coma, or higher-order root mean square error between the groups (all P > 0.05), but the WF-guided group had less trefoil compared with the WF-optimized group (0.14±0.07 vs. 0.20±0.09; P   0.05).Conclusions: Wavefront-guided and WF-optimized LASIK using the Alcon WaveLight Allegretto Eye-Q 400-Hz excimer laser platform provide similar results in myopic patients; however, the WF-guided approach may yield small gains in visual acuity, predictability, and HOAs.Financial Disclosure(s): Proprietary or commercial disclosure may be found after the references.

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One-Year Outcomes from a Prospective, Randomized, Eye-to-Eye Comparison of Wavefront-Guided and Wavefront-Optimized LASIK in Myopes – Corrected Proof

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Objective: To compare wavefront (WF)-guided and WF-optimized LASIK in myopes.Design: Prospective, randomized, eye-to-eye study.Participants: A total of 72 eyes of 36 participants with myopia with or without astigmatism.Methods: Participants were randomized to receive WF-guided or WF-optimized LASIK with the WaveLight Allegretto Eye-Q 400-Hz excimer laser platform (Alcon, Inc., Hüenberg, Switzerland). LASIK flaps were created using the 150-kHz IntraLase iFS (Abbott Medical Optics, Santa Ana, CA). Evaluations included measurement of uncorrected distance visual acuity (UDVA), corrected distance visual acuity (CDVA), <5% and <25% contrast sensitivity, and WF aberrometry. Patients also completed a validated questionnaire detailing symptoms on a quantitative scale.Main Outcome Measures: Safety, efficacy, predictability, refractive error, UDVA, CDVA, contrast sensitivity, and higher-order aberrations (HOAs).Results: The frequency with which the WF-guided and WF-optimized groups achieved postoperative UDVA of ≥20/16 or ≥20/20 and the frequency with which the groups lost 1 or 2 or more lines or maintained their preoperative CDVA were not statistically different from each other (all P > 0.05). The frequency with which the WF-guided group attained a refractive error within ±0.25 diopters of emmetropia was higher than in the WF-optimized group (67.6%, 95% confidence interval [CI], 50.4–84.8 vs. 41.2%, 95% CI, 23.2–59.2; P = 0.03). The WF-guided group’s mean UDVA was better than the WF-optimized group’s UDVA by approximately 1 Early Treatment Diabetic Retinopathy Study line (−0.17±0.11 logarithm of the minimum angle of resolution [logMAR], slightly <20/12 Snellen vs. −0.13±0.12, slightly >20/16; P = 0.05). There were no statistically significant differences in contrast sensitivity, astigmatism, coma, or higher-order root mean square error between the groups (all P > 0.05), but the WF-guided group had less trefoil compared with the WF-optimized group (0.14±0.07 vs. 0.20±0.09; P   0.05).Conclusions: Wavefront-guided and WF-optimized LASIK using the Alcon WaveLight Allegretto Eye-Q 400-Hz excimer laser platform provide similar results in myopic patients; however, the WF-guided approach may yield small gains in visual acuity, predictability, and HOAs.Financial Disclosure(s): Proprietary or commercial disclosure may be found after the references.

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The Cost of Glaucoma Care Provided to Medicare Beneficiaries from 2002 to 2009 – Corrected Proof

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Purpose: To estimate payments for glaucoma care among Medicare beneficiaries from 2002 to 2009.Design: Database study.Participants: Data from a 5% random sample of Medicare billing information from 2002 to 2009.Methods: Medicare beneficiaries, aged 65 years or older, with both Parts A and B fee-for-service (FFS) enrollment comprised the annual denominator. For each year, we included those with a defined glaucoma diagnostic code linked to a glaucoma visit, diagnostic test, or laser/surgical procedure. Open-angle, angle-closure, and other glaucoma were categorized separately. Claims were classified into glaucoma care, other eye care, and other medical care.Main Outcome Measures: Cost of glaucoma care in the Medicare Fee-for-Service Population.Results: In 2009, total glaucoma payments by Medicare were $37.4 million for this subset, for an overall estimated cost of $748 million, or 0.4% of an estimated cost of $192 billion for all Medicare FFS payments. Office visits comprised approximately one half, diagnostic testing was approximately one-third, and surgical and laser procedures were approximately 10% of glaucoma-related costs. Coded open-angle glaucoma (OAG) and OAG suspects accounted for 87.5% of glaucoma costs, whereas cost per person was highest in “other glaucoma.” In 2009, <3% of patients with OAG underwent incisional surgery and approximately 5% had laser trabeculoplasty. Laser iridotomy was the highest cost category among patients with angle-closure glaucoma, whereas office visits was the highest cost category among the “other glaucoma” group. The total cost of nonglaucoma eye care for patients with glaucoma was 67% higher than their glaucoma care costs; these were chiefly costs for cataract surgery and treatment of retinal diseases. From 2002 to 2009, FFS glaucoma care costs calculated in 2009 dollars were stable and cost per person per year in 2009 dollars decreased from $242 to $228 (P = 0.01 by test for linear trend).Conclusions: Annual glaucoma care costs per person decreased in constant dollars from 2002 to 2009. Cataract and retinal eye care for patients with glaucoma substantially exceeded the cost of their glaucoma care each year. Visit payments represented the largest category of costs.Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

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The Clinical Effect of Homozygous ABCA4 Alleles in 18 Patients – Corrected Proof

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Purpose: To describe the phenotypic presentation of a cohort of individuals with homozygous disease-associated ABCA4 variants.Design: Retrospective case series.Participants: Eighteen affected individuals from 13 families ascertained from a total cohort of 214 families with ABCA4-related retinal disease presenting to a single center.Methods: A detailed history was obtained, and color fundus photography, autofluorescence (AF) imaging, optical coherence tomography (OCT), and electrophysiologic assessment were performed. Phenotypes based on ophthalmoscopy, AF, and electrophysiology were assigned using previously reported characteristics. ABCA4 mutation detection was performed using the ABCR400 microarray (Asper Biotech, Tartu, Estonia) and high-throughput DNA sequencing, with direct sequencing used to assess segregation.Main Outcome Measures: Detailed clinical, electrophysiologic, and molecular genetic findings.Results: Eleven disease-associated homozygous ABCA4 alleles were identified, including 1 frame shift, 2 stops, 1 intronic variant causing splice-site alteration, 2 complex missense variants, and 5 missense variants: p.Glu905fsX916, p.Arg1300X, p.Gln2220X, c.4253+4 C>T, p.Leu541Pro and p.Ala1038Val (homozygosity for complex allele), p.Val931Met and p.Arg1705Gln (complex allele), p.Arg212Cys, p.Cys1488Arg, p.Arg1640Trp, p.Gly1961Glu, and p.Leu2027Phe. Eight of these 11 homozygous alleles have not been reported previously. Six of 7 patients with homozygous null alleles had early-onset (<10 years) disease, with all 7 having a severe phenotype. Two patients with homozygous missense variants (p.Leu541Pro and p.Ala1038Val [complex], and p.Arg1640Trp) presented with a severe phenotype. Three patients with homozygous p.Gly1961Glu had adult-onset disease and a mild phenotype. One patient with homozygous p.Leu2027Phe showed a spared fovea and preserved visual acuity.Conclusions: The phenotypes represented in patients identified as homozygous for presumed disease-associated ABCA4 variants gives insight into the effect of individual alleles. Null alleles have severe functional effects, and certain missense variants are similar to nulls, suggesting complete abrogation of protein function. The common alleles identified, p.Gly1961Glu and p. Leu2027Phe, both have a mild structural and functional effect on the adult retina; the latter is associated with relatively retained photoreceptor architecture and function at the fovea.Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

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