Faculty Bibliography

Purpose : To evaluate the diagnostic yield and clinical impact of the SPARK/Invitae gene panel in patients with known or suspected inherited degenerative retinal disease, in comparison with traditional clinical assessments. Methods : Patients of the authors' clinical practices obtained genetic screening at no charge via the SPARK/Invitae ID your IRD genetic testing panel, which ranged from 248 genes to 293 genes. Over 16 months, tests were submitted for 87 patients and results were available for 70 patients. Clinical diagnoses prior to submitting the gene panel . By continuing to use our website, you are agreeing to included retinitis pigmentosa; Stargardt disease; Best vitelliform dystrophy; Leber our privacy policy. congenital amaurosis; choroideremia; achromatopsia; cone-rod dystrophy; congenital stationary night blindness; occult macular dystrophy; and familial dominant drusen in addition to patients with normal clinical findings and unclear diagnoses. Results : Of 70 patients, SPARK/Invitae considered the results ''Positive or Potentially Positive'' in 24 cases (34.3%), Carrier in 16 cases (22.9%) and ''Uncertain'' in 30 cases (42.9%). Uncertain results comprised patients with only Variants of Uncertain Significance. Patients categorized as a Carrier by SPARK/Invitae but who demonstrated pathogenic genetic changes correlating to the clinical diagnosis were considered to be in agreement with the clinical impression. The genetic diagnosis agreed with the clinical diagnosis in 30/70 (42.9%) total patients. Test results were consistent with the clinical impression in 13/26 (50.0%) retinitis pigmentosa cases, 6/8 (75.0%) Stargardt patients, 3/7 (42.9%) cone-rod dystrophy cases, and 2/4 (50.0%) Best vitelliform dystrophy patients. Gene testing helped elucidate diagnoses in two patients with unclear clinical impressions: one panel showed autosomal recessive achromatopsia and the other showed a carrier state for autosomal recessive retinitis pigmentosa. Of four patients with normal clinical exams, none had diagnostic results: all showed Uncertain findings. Conclusions : The SPARK/Invitae gene panel provided a genetic diagnosis consistent with the clinical impression in about 40 percent of patients. Retinitis pigmentosa and Stargardt disease were the most common clinical diagnoses and the diagnoses most often confirmed by testing. Genetic screening also assisted in clarifying unknown diagnoses for two patients

Purpose : To assess risk factors for development of endophthalmitis following open globe injury. Methods : A retrospective chart review of all patients treated for open globe injury at the University of Michigan from January 2000 through July 2017 was conducted. Exclusion criteria included intravitreal injection or intraocular surgery in the 30 days prior to injury or less than 30 days of follow-up. A total of 586 out of 993 eyes were included in the study. The main outcome measure was the rate of endophthalmitis in these eyes. Results : 25/586 eyes (4.3%) presented with endophthalmitis, or developed endophthalmitis following globe closure. Of these, 12/25 eyes (48.0%) presented with endophthalmitis and 13/25 eyes (52.0%) developed endophthalmitis after globe closure. Multivariate logistic regression analysis identified time to globe repair (OR 4.5, CI 1.9-10.7, p = 0.0008), zone I injury (OR 3.6, CI 1.1-11.0, p = 0.0282), and need for additional surgery (OR 5.5, CI 1.5-19.7, p = 0.0092) as factors associated with increased risk of developing endophthalmitis. Subconjunctival antibiotics (OR 0.3, CI 0.1-0.7, p = 0.0036) were associated with decreased risk of developing endophthalmitis. Conclusions : Prompt closure of the globe and use of subconjunctival antibiotics may reduce the risk of endophthalmitis in open globe injuries. Furthermore, a one-time dose of prophylactic antibiotics with same day discharge and delayed IOFB removal with intravitreal injection of antibiotics did not increase the rate of endophthalmitis. Open globe injuries can be visually devastating and understanding what factors predict and protect against endophthalmitis is paramount to achieving the best possible visual outcomes

PURPOSE/OBJECTIVE:To determine which spectral domain optical coherence tomography biomarkers of idiopathic macular hole (MH) correlate with the postoperative best-corrected visual acuity (BCVA) in anatomically closed MH. METHODS:Retrospective analysis of spectral domain optical coherence tomography scans of 44 patients presenting with MH followed for a mean of 17 months. Widths of MH aperture, base, and ellipsoid zone disruption were calculated from presenting foveal spectral domain optical coherence tomography B-scans. Macular hole base area and ellipsoid zone disruption area were calculated through the custom in-house software. RESULTS:Poorer postoperative BCVA correlated with increased preoperative choroidal hypertransmission (r = 0.503, P = 0.0005), minimum diameter (r = 0.491, P = 0.0007), and base diameter (r = 0.319, P = 0.0348), but not with preoperative ellipsoid zone width (r = 0.199, P = 0.2001). Applying en-face analysis, the BCVA correlated weakly with preoperative ellipsoid zone loss area (r = 0.380, P = 0.013), but not with preoperative MH base area (r = 0.253, P = 0.1058). CONCLUSION/CONCLUSIONS:Increased MH minimum diameter, base diameter, base area, and choroidal hypertransmission are correlated with a poorer postoperative BCVA. Ellipsoid zone loss measurements were not consistently correlated with a BCVA. Choroidal hypertransmission width may be an easy-to-visualize predictive imaging biomarker in MH surgery.

Background/Aims/UNASSIGNED:To determine the rate of endophthalmitis and assess risk factors for development of endophthalmitis following open globe injury (OGI). Methods/UNASSIGNED:A retrospective chart review of all patients treated for OGI at the University of Michigan from January 2000 to July 2017 was conducted. Exclusion criteria included intravitreal injection or intraocular surgery in the 30 days prior to injury or less than 30 days of follow-up. A total of 586 out of 993 open globe injuries were included in the study. The main outcome measure was the rate of endophthalmitis. Results/UNASSIGNED:In this study, 25/586 eyes (4.3%) had endophthalmitis. Of these, 12/25 eyes (48.0%) presented with endophthalmitis and 13/25 eyes (52.0%) developed endophthalmitis after globe closure. Multivariate analysis identified time to globe repair (OR 4.5, CI 1.9-10.7, p = 0.0008), zone I injury (OR 3.6, CI 1.1-11.0, p = 0.0282), and need for additional surgery (OR 5.5, CI 1.5-19.7, p = 0.0092) as factors associated with increased risk of developing endophthalmitis. Subconjunctival antibiotic injection at the time of globe closure (OR 0.3, CI 0.1-0.7, p = 0.0036) was associated with decreased risk of developing endophthalmitis. Conclusion/UNASSIGNED:Prompt globe closure and subconjunctival antibiotics may reduce the risk of endophthalmitis in OGI. Furthermore, our practice of a one-time dose of systemic prophylactic antibiotics, and intravitreal antibiotics if intraocular foreign body (IOFB) removal is delayed, was not found to increase the rate of endophthalmitis.

Purpose To evaluate the diagnostic yield and clinical impact of the SPARK/Invitae 248 gene panel in patients with known or suspected inherited degenerative retinal disease, in comparison with traditional clinical assessments including ERG testing. Methods Patients were drawn from the clinical practices of the authors. Genetic screening was provided by means of the SPARK/Invitae 248-gene panel at no charge to patients. Over the past year, results are available for 18 patients. Clinical diagnoses were Best vitelliform dystrophy (definite in one patient, suspected in three patients); retinitis pigmentosa (five affected patients, one likely female carrier); possible Stargardt disease (five patients); and one each with Leber congenital amaurosis, choroideremia, nyctalopia, and Norrie disease. Results Of the 18 studies returned, results were deemed by Invitae ''Positive'' in nine and ''Uncertain'' in nine. The genetic diagnosis agreed with the clinical diagnosis in eight cases (including two patients diagnosed with retinitis pigmentosa with homozygous mutations in USH2A, and one patient with the diagnosis of retinitis pigmentosa with compound heterozygotic mutations in NR2E3, which is also associated with enhanced S-cone syndrome). One patient with macular degeneration of uncertain etiology had a deletion in TPP1, which codes for ceroid lipofuscinosis. The remaining nine patients all returned heterozygous mutations considered ''variations of uncertain significance'' (VUS) ranging from two to eight different genes. Heterozygous VUS in ABCA4 were noted in two patients with the clinical diagnosis of Stargardt disease and in one with the clinical diagnosis of Best disease. Conclusion The SPARK/Invitae 248-gene panel provided a genetic diagnosis consistent with the clinical diagnosis in about half of cases and was diagnostic in one case where the clinical diagnosis was unclear. Retinitis pigmentosa and Stargardt disease were the most common genetic diagnoses. No cases of Leber congenital amaurosis were detected by genetic testing which had been misdiagnosed clinically.

PURPOSE/OBJECTIVE:To report a rare case of vitreous cavity-Tenon capsule fistula formation after removal of a symptomatic hydrogel scleral buckle. METHODS:Case report. RESULTS:A 43-year-old man presented with chronic headache and involuntary gaze deviation for over 1 year after hydrogel scleral buckle surgery 25 years prior. After removal of the scleral buckle, the patient developed a fluid-filled inflation of the buckle capsule, surrounding a previously noted area of severe scleral thinning. Ocular ultrasonography suggested a fistulous connection between the vitreous cavity and the sub-Tenon space in the area of scleral thinning. There was resolution of diplopia and headache postoperatively, with stability of the fluid collection on clinical examination. Because of high risk of further surgery and resolution of the patient's symptoms, conservative management was elected. CONCLUSION/CONCLUSIONS:This is the first report, to the best of our knowledge, of Tenon capsule-vitreous cavity fistula formation after scleral buckle explantation. Because of innate ability to expand, as well as tendency to become friable, hydrogel buckles have a higher risk of requiring removal and of complications from explantation, respectively. Our patient experienced relief of symptoms, without complication from the fistula, and was successfully managed conservatively.

PURPOSE/OBJECTIVE:To assess whether publication of Comparison of Age-related macular degeneration Treatment Trial (CATT) results and introduction of aflibercept to the marketplace affected intravitreal bevacizumab and ranibizumab utilization. DESIGN/METHODS:Retrospective analysis of treatment patterns. METHODS:We calculated weekly bevacizumab and ranibizumab utilization during 3 timeframes: (1) before CATT publication, (2) between CATT publication (4/28/2011) and assignment of a unique aflibercept billing code (1/1/2013), and (3) afterwards for 164188 Medicare beneficiaries with neovascular macular degeneration receiving ≥1 anti-Vascular Endothelial Growth Factor injections from 1/1/2008 to 12/31/2014. We identified ophthalmologists who predominantly (≥80%) administered bevacizumab or ranibizumab, and evaluated changes in preferences over the 3 periods. We replicated analyses on 881381 commercially-insured beneficiaries. RESULTS:Among 317 ophthalmologists administering predominantly ranibizumab to Medicare beneficiaries pre-CATT, 221 (69.7%) reduced ranibizumab utilization post-CATT, whereas 96 (30.3%) continued using ranibizumab ≥80% of the time. Findings were reversed among 1041 ophthalmologists who predominantly administered bevacizumab pre-CATT-777 (74.6%) continued bevacizumab-predominant use while 264 (25.4%) reduced bevacizumab utilization post-CATT. Among the 145 ophthalmologists who predominantly administered ranibizumab before aflibercept's availability, 77 (53.1%) reduced ranibizumab utilization and 68 (46.9%) continued using ranibizumab ≥80% of the time after aflibercept became available. Corresponding numbers among the 909 ophthalmologists who predominantly administered bevacizumab pre-aflibercept were 381 (41.9%) reducing and 528 (58.1%) continuing bevacizumab-predominant use. Similar results were observed for commercially-insured patients. CONCLUSIONS:Many ophthalmologists who favored ranibizumab switched to bevacizumab after CATT publication while most who favored bevacizumab prior to CATT publication continued favoring it afterwards. Aflibercept's introduction had little impact on preferences for ranibizumab or bevacizumab.

BACKGROUND:Inadequate screening of treatment-warranted retinopathy of prematurity (ROP) can lead to devastating visual outcomes. Especially in resource-poor communities, the use of an affordable, portable, and easy to use smartphone-based non-contact fundus photography device may prove useful for screening for high-risk ROP. This study evaluates the feasibility of screening for high-risk ROP using a novel smartphone-based fundus photography device, RetinaScope. METHODS:Retinal images were obtained using RetinaScope on a cohort of prematurely born infants during routine examinations for ROP. Images were reviewed by two masked graders who determined the image quality, the presence or absence of plus disease, and whether there was retinopathy that met predefined criteria for referral. The agreement between image-based assessments was compared to the gold standard indirect ophthalmoscopic assessment. RESULTS:Fifty-four eyes of 27 infants were included. A wide-field fundus photograph was obtained using RetinaScope. Image quality was acceptable or excellent in 98% and 95% of cases. There was substantial agreement between the gold standard and photographic assessment of presence or absence of plus disease (Cohen's κ = 0.85). Intergrader agreement on the presence of any retinopathy in photographs was also high (κ = 0.92). CONCLUSIONS:RetinaScope can capture digital retinal photographs of prematurely born infants with good image quality for grading of plus disease.

PURPOSE/OBJECTIVE:To describe the range of ocular manifestations in cutis marmorata telangectatica congenita (CMTC). DESIGN/METHODS:Multicenter, retrospective, nonconsecutive case series. PARTICIPANTS/METHODS:Patients with a diagnosis of CMTC referred for ophthalmologic evaluation between January 1, 2015, and December 31, 2018. METHODS:Evaluation of ocular findings at presentation, systemic manifestations suggestive of a diagnosis of CMTC, genetic testing, and visual outcomes after treatment. MAIN OUTCOME MEASURES/METHODS:Visual acuity, findings on ophthalmoscopy, and results of fluorescein angiography. RESULTS:Nine patients with CMTC diagnosed clinically based on stereotypical cutaneous vascular malformations were included. The median age at presentation was 8 weeks (range, 2 weeks-4 years). Six patients were female and 3 were male. Avascular retina was identified on dilated fundus examination, fluorescein angiography, or both in 11 eyes of 6 patients. Retinal neovascularization was present bilaterally in 2 patients at presentation. One patient demonstrated retinal venous tortuosity, and another patient showed mild straightening of nasal retinal vessels in both eyes. Two patients (2 eyes) demonstrated retinal detachment (RD). Both were managed surgically. One infant demonstrated RD, whereas the other child showed extensive neovascularization and later progressed to combined tractional-rhegmatogenous detachment. A unique constellation of lacy peripheral capillary anomalies with prominent terminal vascular bulbs was noted in 3 patients. Granular pigment abnormalities were noted in the macula in 5 patients. Two patients demonstrated glaucoma, 1 requiring surgical intervention. Two patients demonstrated features of Adams-Oliver syndrome, with genetic testing identifying a Notch1 mutation in 1 patient. CONCLUSIONS:Retinal vascular abnormalities in CMTC may occur more frequently than recognized previously. Given the variability of ocular involvement and the potential for rapidly progressive retinal vascular abnormalities and development of RD, complete ophthalmologic evaluation including measurement of intraocular pressure, gonioscopy, dilated fundus examination, and fluorescein angiography is recommended in infants with suspected CMTC shortly after birth. The distinct pattern of lacy capillary anomalies with prominent terminal bulbs seen in CMTC has not been described in other syndromes of vascular dysgenesis. Therefore, ophthalmic examination may be a valuable method to distinguish CMTC from other disorders demonstrating similar dermatologic and systemic manifestations.