Effects of Lidocaine on Mitomycin C Cytotoxicity.

PURPOSE: Intra-Tenon or subconjunctival injection of a solution of mitomycin C (MMC) and 1% preservative-free lidocaine (as an anesthetic) has gained popularity for its use in trabeculectomy, a filtering surgery for glaucoma. To our knowledge, no studies have analyzed the impact of lidocaine on the cytotoxic effects of MMC in this setting. This study was conducted to evaluate in vitro fibroblast cytotoxicity to a solution of MMC (0.2 mg/ml) and 1% preservative-free lidocaine. DESIGN: Experimental study. PARTICIPANTS: Nonhuman subject research. METHODS: Cultured human conjunctival fibroblasts were incubated in phosphate-buffered saline (PBS) (control), MMC (0.2 mg/ml), a mixture of 0.2 mg/ml MMC + 1% preservative-free lidocaine, or 1% preservative-free lidocaine. Samples were taken at 2, 5, 10, 30, and 60 minutes, and a 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT) assay with photoabsorbance testing was used to assess conjunctival cell viability. MAIN OUTCOME MEASURE: Mean photoabsorbance. RESULTS: Mean photoabsorbance across all time intervals was 0.680 for solutions incubated in PBS, 0.642 for MMC, 0.612 for MMC + 1% preservative-free lidocaine, and 0.605 for 1% preservative-free lidocaine. A 2-way analysis of variance analyzing solution, time, and solution-time interaction on photoabsorbance showed that PBS was least cytotoxic and an optimal control for this study. Tukey post hoc comparisons showed that MMC was more cytotoxic than PBS (P < 0.001). However, both MMC + 1% preservative-free lidocaine and 1% preservative-free lidocaine were more cytotoxic than MMC and PBS (P < 0.01 for all). No significant differences in cytotoxicity comparing lidocaine-containing solutions were observed. CONCLUSIONS: In this in vitro study, we found an increase in cytotoxicity when MMC (0.2 mg/ml) was combined with 1% preservative-free lidocaine. We note that lidocaine did not inhibit MMC cytotoxicity and exhibited a significant cytotoxic effect on its own.

Association of Dry Eye Disease With Dyslipidemia and Statin Use.

PURPOSE: To determine whether an association exists between dry eye disease (DED) and statin use and/or dyslipidemia. DESIGN: Retrospective, case-control study. METHODS: Setting: University of North Carolina (UNC)-affiliated healthcare facilities. STUDY POPULATION: 72,931 patients seen at UNC ophthalmology clinics over a 10-year period. MAIN OUTCOME MEASURES: Odds ratios (ORs) calculated between DED and a history of low, moderate, or high-intensity statin use; and ORs calculated between DED and abnormal lipid panel values. RESULTS: Total of 39,336 individuals (53.9% female) were analyzed after exclusion of individuals with confounding risk factors for DED. Of these, 3,399 patients (8.6%) carried a diagnosis of DED. Low-, moderate-, and high-intensity statin regimens were used by 751 subjects (1.9%), 2,655 subjects (6.8%), and 1,036 subjects (2.6%). Lipid abnormalities were identified as total cholesterol >200 mg/dL, 4,558 subjects (11.6%); high-density lipoprotein (HDL) <40 mg/dL, 2,078 subjects (5.3%); low-density lipoprotein (LDL) >130 mg/dL, 2,756 subjects (7.0%); and triglycerides (TGs) >150 mg/dL, 2,881 subjects (7.3%). The odds ratios (OR) of carrying a diagnosis of DED given the presence of low-, moderate-, and high-intensity statin use were 1.39 (95% confidence interval [CI]: 1.13-1.72); OR 1.47 (95% CI: 1.30-1.65), and OR 1.46 (95% CI: 1.21-1.75), respectively. The OR of carrying a diagnosis of DED given the presence of total cholesterol >200 mg/dL, HDL <40 mg/dL, LDL >130 mg/dL, and TGs >150 mg/dL were 1.66 (95% CI: 1.52-1.82), 1.45 (95% CI: 1.26-1.67), 1.55 (95% CI: 1.39-1.74), and 1.43 (95% CI: 1.27-1.61), respectively. CONCLUSIONS: A history of statin use or dyslipidemia is associated with an increased odds of having a DED diagnosis. Further studies are needed to determine whether statin use and/or dyslipidemia increases the risk of DED.

Office-based Air-Fluid Exchange for Diabetic Post-Operative Vitreous Cavity Hemorrhage.

Post-operative vitreous cavity hemorrhage (POVCH) is observed in 6-75% of eyes undergoing pars plana vitrectomy (PPV) for proliferative diabetic retinopathy (PDR). We describe our technique for office-based Air fluid exchange (AFX) in the treatment of POVCH. Sixteen eyes (15 patients) with PDR and POVCH undergoing office-based AFX between January 2006 and November 2016 were retrospectively identified. The pre- and post- procedure visual acuity (VA) and complications were compared between eyes with and without traction retinal detachment (TRD). Medicare charges for office-based AFX versus PPV were also analyzed. Mean (± standard deviation [SD]) age at the time of AFX was 55.31 (± 8.02) years. Nine eyes (56.25%) had TRD prior to PPV and 11 eyes (68.75%) were pseudophakic. The improvements in mean (±SD) logMAR VA at the last postoperative visit (3 - 8 months) were 1.38 (± 0.99), 0.82 (± 0.91) and 2.09 (± 0.53) in all eyes, TRD eyes and non-TRD eyes, respectively. Complications included cataract progression, hypotony, and recurrence of TRD and ghost cell glaucoma. The total cost of outpatient AFX was $1,409.59 less than that of PPV. Office-based AFX is a cost-effective alternative treatment for non-clearing diabetic POVCH with an acceptable risk profile.

Correction: Arterial tortuosity syndrome: 40 new families and literature review.

In the published version of this paper the author Neus Baena's name was incorrectly given as Neus Baena Diez. This has now been corrected in both the HTML and PDF versions of the paper.

Corneal hysteresis in post-radial keratotomy primary open-angle glaucoma.

PURPOSE: Corneal hysteresis (CH) is a corneal biomechanical property measured by the ocular response analyzer (ORA). It is associated with primary open-angle glaucoma development, progression, and severity as well as intraocular pressure (IOP) measurement. Decreases in CH and changes in IOP measurements have been described for laser-assisted refractive surgery; however, patients with prior radial keratotomy (RK) have not been examined. We have performed a cohort study examining CH and intraocular pressure measurements (Goldmann applanation and ORA values including Goldmann-correlated and cornea-compensated IOP [adjusted for corneal hysteresis]) in RK patients and myopic controls with POAG. METHODS: Eighty POAG patients (28 RK and 52 myopic controls) were recruited. Central corneal thickness (CCT), prostaglandin analogue (PGA) use, perimetric stage, and history of cataract and glaucoma filtration surgery were assessed through chart review. Participants underwent testing with the ORA (yielding measures of CH, cornea-compensated [IOPcc], Goldmann-correlated IOP [IOPgc], and corneal resistance factor [CRF]), Goldmann applanation, A-scan for axial length (AL), and corneal topography. Slit lamp exam was performed to assess for number of incisions in RK patients. RESULTS: Adjusting for AL and CCT, CH was significantly lower in the RK group with an estimated difference of 0.8585 mmHg (p = 0.0112). Cornea-compensated intraocular pressure was significantly higher in the RK group after controlling for Goldmann applanation, AL, and CCT (2.35 mmHg difference, p < 0.001). Corneal resistance factor and IOPgc were not significantly different. A correlational analysis did not reveal a significant correlation between numbers of RK incisions and CH. CONCLUSIONS: We report significant differences, with lower CH and higher IOPcc, when comparing eyes with glaucoma and either a history of RK or myopia. These findings may aid in establishing normative decreases in CH with RK and POAG and indicate a possible under-estimation of pressure in RK patients.

A Database Study of Visual Outcomes and Intraoperative Complications of Postvitrectomy Cataract Surgery.

PURPOSE: To analyze the visual outcomes and rate of intraoperative complications of phacoemulsification surgery after prior pars plana vitrectomy (PPV). DESIGN: Retrospective, multicenter database study. PARTICIPANTS: Eyes that underwent phacoemulsification between June 2005 and March 2015 at 8 sites in the United Kingdom. METHODS: Study eyes were classified as vitrectomized (prior PPV group) or nonvitrectomized (reference group) depending on the vitreous state at the time of cataract surgery. Eyes with multiple intraocular surgeries or history of ocular diseases known to cause cataract progression or increased risk of intraoperative complications during phacoemulsification were excluded. MAIN OUTCOME MEASURES: Logarithm of the minimum angle of resolution (logMAR) visual acuity (VA), rate of intraoperative complications, and time interval to cataract surgery. RESULTS: Eyes in the prior PPV group (n = 2221) had worse preoperative logMAR VA (0.96±0.60 vs. 0.62±0.52, P < 0.0001), were from younger patients, and had longer axial lengths than the nonvitrectomized group (n = 136 533). At all postoperative time points measured up to 24 weeks, mean vision was poorer in the prior PPV group (0.41±0.47 vs. 0.17±0.29 at 4-12 weeks, P < 0.0001) and a smaller proportion of eyes achieved postoperative VA ≤0.30 logMAR (Snellen, ≥20/40) (60.8% vs. 86.5% at 4-12 weeks, P < 0.0001). The rate of posterior capsular rupture was not different between the prior PPV (1.5%) and the nonvitrectomized (1.7%) groups, but the incidences of zonular dialysis (1.3% vs. 0.6%) and dropped nuclear fragments (0.6% vs. 0.2%) were higher in the prior PPV group (P < 0.0001). The mean time interval between PPV and cataract surgery was 399 days. CONCLUSIONS: We found a significant improvement in VA with postvitrectomy cataract surgery. However, compared with eyes without prior PPV, there was a worse mean postoperative vision of 0.2 logMAR units, a higher rate of zonular dialysis and dropped nuclear fragments, and a similar rate of posterior capsule rupture.

Repeat Intravitreal Dexamethasone Implant for Refractory Cystoid Macular Edema in Syphilitic Uveitis.

PURPOSE: To report the successful utilization of adjunctive repeat intravitreal corticosteroid therapy for the treatment of cystoid macular edema in syphilis-related uveitis. METHODS/PATIENTS: An HIV-positive patient with treated ocular syphilis who developed refractory cystoid macular edema (CME) was treated with repeat intravitreal corticosteroid therapy including dexamethasone intravitreal implants. RESULTS: Treatment led to the resolution of CME and improvement in visual acuity. CONCLUSIONS: Intravitreal corticosteroid therapy may be a viable adjunctive treatment for refractory CME in patients with treated syphilitic uveitis. Corticosteroid-induced exacerbation of infection is unlikely in patients with an adequate serologic treatment response.

Arterial tortuosity syndrome: 40 new families and literature review.

PURPOSE: We delineate the clinical spectrum and describe the histology in arterial tortuosity syndrome (ATS), a rare connective tissue disorder characterized by tortuosity of the large and medium-sized arteries, caused by mutations in SLC2A10. METHODS: We retrospectively characterized 40 novel ATS families (50 patients) and reviewed the 52 previously reported patients. We performed histology and electron microscopy (EM) on skin and vascular biopsies and evaluated TGF-ß signaling with immunohistochemistry for pSMAD2 and CTGF. RESULTS: Stenoses, tortuosity, and aneurysm formation are widespread occurrences. Severe but rare vascular complications include early and aggressive aortic root aneurysms, neonatal intracranial bleeding, ischemic stroke, and gastric perforation. Thus far, no reports unequivocally document vascular dissections or ruptures. Of note, diaphragmatic hernia and infant respiratory distress syndrome (IRDS) are frequently observed. Skin and vascular biopsies show fragmented elastic fibers (EF) and increased collagen deposition. EM of skin EF shows a fragmented elastin core and a peripheral mantle of microfibrils of random directionality. Skin and end-stage diseased vascular tissue do not indicate increased TGF-ß signaling. CONCLUSION: Our findings warrant attention for IRDS and diaphragmatic hernia, close monitoring of the aortic root early in life, and extensive vascular imaging afterwards. EM on skin biopsies shows disease-specific abnormalities.

Cataract Surgery Outcomes in Eyes With Primary Epiretinal Membrane.

Importance: Primary epiretinal membrane (ERM) is a common retinal disorder with a prevalence of 4% to 18.5%. Although ERM and cataracts commonly occur together, to our knowledge, no studies have investigated the outcome of cataract surgery alone in this setting. Objective: To analyze the visual outcome and cystoid macular edema risk with cataract surgery in eyes with primary ERM. Design, Setting, and Participants: In this retrospective clinical database study, data were collected from July 2003 to March 2015 from 8 locations in the United Kingdom. Cataract surgery data of 217 557 eyes were extracted from the electronic medical record of the UK National Health Service. After exclusion of 57 561 eyes with combined surgery, prior vitrectomy, copathology, and complications, 812 eyes with primary ERM and 159 184 reference eyes were analyzed. Main Outcomes and Measures: We report on visual acuity (VA), the incidence of cystoid macular edema, and the need for ERM surgery. Results: The mean (SD) age of patients in the ERM group was 73.7 (9.23) years, and 395 of 812 were men (46.8%). The mean (SD) age of patients in the reference group was 74.4 (12.19) years, and 65 265 of 159 184 were men (41%). Epiretinal membrane eyes assessed at 4 to 12 weeks postoperatively gained 0.27 (0.32) logMAR (approximately 3 Snellen lines), with 200 of 448 (44.6%) improving by 0.30 logMAR or more (≥3 Snellen lines) and 32 of 448 (7.1%) worsening by 0.30 logMAR or more. Reference eyes gained a mean (SD) of 0.44 (0.26) logMAR (approximately 4 Snellen lines), with 48 583 of 77 408 (62.8%) improving by 0.30 logMAR or more and 2125 of 77 408 (2.7%) worsening by 0.30 logMAR or more. Although all eyes with preoperative VA of 20/40 or less improved, only reference eyes with preoperative VA of more than 20/40 showed improvement. Cystoid macular edema developed in 57 of 663 ERM eyes (8.6%) (95% CI, 6.69-10.98) and 1731 of 125 435 reference eyes (1.38%) (95% CI, 1.32-1.45) (P < .001). Epiretinal membrane surgery was performed in 43 of 663 (6.5%) ERM eyes. Conclusions and Relevance: On average, VA improved 0.27 logMAR (approximately 3 Snellen lines) in eyes with ERM. Eyes with ERM and VA of 20/40 or less showed more benefit after cataract surgery than those with better preoperative vision. However, compared with eyes without ERM, higher rates of cystoid macular edema and a lower postoperative VA gain were noted.

Ophthalmic findings in patients with arterial tortuosity syndrome and carriers: A case series.

INTRODUCTION: Arterial tortuosity syndrome (ATS) is a rare autosomal recessive disease hallmarked by tortuosity, stenosis, and aneurysm development of large- and medium-sized arteries. Mutations in SLC2A10, a gene that encodes the facilitative glucose transporter GLUT10, cause ATS. Several case reports have noted associated ophthalmic findings such as keratoconus, keratoglobus, and myopia without detailed descriptions or standardized examinations. We report the ophthalmic findings in a cohort of compound heterozygous ATS patients and heterozygous carriers of SLC2A10 mutations. METHODS: Five ATS patients and three carriers were identified through an ATS specialty clinic at the Arkansas Children's Hospital in Little Rock, Arkansas. Patients underwent complete eye examinations, including corneal pachymetry, topography, and optical coherence tomography when indicated. RESULTS: All five patients with ATS had myopia and thin corneas with an average central corneal thickness of 426 µm, and three had corneal ectasia, two with early keratoconus and one with keratoglobus and deep stromal corneal opacities. One patient had bilateral high irregular astigmatism, and one had unilateral high regular astigmatism. All carriers had myopia, one had corneal thinning, and one developed keratectasia in one eye many years after laser-assisted in situ keratomileusis (LASIK) surgery. CONCLUSION: We document a spectrum of ophthalmic manifestations of ATS with universal findings of myopia, corneal thinning, and a propensity for corneal ectasia leading to keratoconus or keratoglobus. Heterozygous carriers may develop keratectasia after corneal refractive surgery. Our data support regular eye examinations for all patients carrying SLC2A10 mutations with follow-up tailored to clinical findings.

Idiopathic Intracranial Hypertension Progressing to Venous Sinus Thrombosis, Subarachnoid Hemorrhage, and Stroke.

Idiopathic intracranial hypertension (IIH) is a syndrome characterized by increased intracranial pressure (ICP), the absence of structural lesions on neuroimaging, and normal cerebrospinal fluid composition. Cerebral venous sinus thrombosis (CVST) is a common cause of increased ICP and can be differentiated from IIH with magnetic resonance venography. We describe a young woman with typical IIH who underwent lumbar puncture and was treated with a short course of high-dose corticosteroids followed by acetazolamide. She subsequently developed CVST, subarachnoid hemorrhage, and stroke. Risk factors that may have resulted in CVST are discussed.

A unique case series of autosomal recessive bestrophinopathy exhibiting multigenerational inheritance.

INTRODUCTION: Autosomal recessive bestrophinopathy (ARB) is a retinal disease caused by biallelic mutations of the BEST1 gene. It has a variable phenotype with white flecks in the retina, multifocal yellow subretinal deposits, macular edema, choroidal neovascularization, hyperopia, and electrophysiological abnormalities. We describe a family with ARB and multigenerational inheritance. METHODS: Three generations of a Middle Eastern family (a woman, one son, and two grandchildren) were evaluated by our ocular genetics team. Eye examinations, fundus photography, and optical coherence tomography (OCT) were performed. Genetic testing was obtained on examined patients and available relatives. RESULTS: The proband demonstrated counting fingers vision and white flecks in the retinal periphery, with macular subretinal fluid (SRF), loss of outer photoreceptor segments, and epiretinal membrane (ERM) on OCT. Two grandchildren demonstrated decreased vision, multifocal yellow subretinal deposits, and SRF on OCT. Two grandchildren examined elsewhere were reported to be similarly affected. A son's examination was normal except for extra-macular scars (from prior toxoplasmosis) and ERM. Genetic history revealed consanguinity and testing showed homozygosity for BEST1 mutations in the proband and two grandchildren c.473G>A/c.473G>A (R218H /R218H) and heterozygosity in two unaffected sons and two unaffected daughters-in-law c.473G>A/WT (p.R218H/WT). DISCUSSION: We present a consanguineous family of five affected individuals with ARB and four confirmed carriers. Their pedigree was consistent with dominant inheritance and incomplete penetrance. Genetic testing clarified the diagnosis and mode of inheritance. We describe the genetic findings, phenotypic variability, and recessive inheritance of an often dominantly inherited mutation as notable elements in their case.

Fungal Keratitis Secondary to Trametes betulina: A Case Report and Review of Literature.

PURPOSE: We report the first case of human infection and keratitis secondary to Trametes betulina, a rare filamentous fungus. METHODS: Clinical examination including external and slit-lamp examination and corneal scrapings with microbiologic evaluation were performed on a patient with chronic allergic conjunctivitis, entropion and a long-standing corneal ulcer resistant to treatment. RESULTS: The culture from the corneal scraping revealed a basidiomycetous fungus which was submitted for identification. DNA extraction with sequencing and analysis of the ITS and D1/D2 regions were performed on the isolate and demonstrated 100% similarity to Lenzites betulina/Trametes betulina. Susceptibility testing demonstrated potent in vitro activity of voriconazole (MIC < 0.03 µg/ml). The patient was treated with voriconazole, and the corneal ulcer and infiltrate resolved. The infection resulted in corneal thinning and a dense central corneal scar. Penetrating keratoplasty was performed 5 months after diagnosis and treatment and revealed stromal scarring without fungal elements. CONCLUSION: This is the first reported case of keratitis caused by Trametes betulina. This organism should be considered in the differential diagnosis for rare filamentous fungal keratitis and its treatment with voriconazole also noted.

Factors Affecting Cirrus-HD OCT Optic Disc Scan Quality: A Review with Case Examples.

Spectral-domain OCT is an established tool to assist clinicians in detecting glaucoma and monitor disease progression. The widespread use of this imaging modality is due, at least in part, to continuous hardware and software advancements. However, recent evidence indicates that OCT scan artifacts are frequently encountered in clinical practice. Poor image quality invariably challenges the interpretation of test results, with potential implications for the care of glaucoma patients. Therefore, adequate knowledge of various imaging artifacts is necessary. In this work, we describe several factors affecting Cirrus HD-OCT optic disc scan quality and their effects on measurement variability.