Search

To demonstrate rapid macular thinning as an early and objective sign of hydroxychloroquine retinopathy. Retrospective case cohort. Cohort of 301 patients receiving long-term hydroxychloroquine therapy at Kaiser Permanente Northern California who underwent a minimum of 4 OCT studies that included Early Treatment Diabetic Retinopathy Study (ETDRS) retinal thickness values over a minimum of 4 years. Creation of sequential retinal thickness plots to show the rate of change in macular thickness within ETDRS regions. Identification of rapid macular thinning, comparison of patients with rapid thinning to those with stable macular thickness, and comparison of rapid thinning patients with and without conventional OCT or 10-2 visual field signs of hydroxychloroquine toxicity. Retina thinning in 219 stable patients receiving long-term hydroxychloroquine therapy averaged (mean ± standard deviation) 0.62 ± 0.45 μm/year, whereas 82 patients showed a period of relatively linear rapid thinning with a loss of 3.75 ± 1.34 μm/year. Of the patients with rapid thinning, 38 eventually demonstrated conventional OCT or 10-2 visual field signs of hydroxychloroquine retinal toxicity. The cumulative retinal thinning in these patients was 25.1 ± 6.2 μm compared with 15.7 ± 4.0 μm in those without conventional toxicity (P < 0.01). Retinal thickness remains stable for many years in most patients receiving long-term hydroxychloroquine therapy, but after a critical point, the retina may begin to thin rapidly. Sequential plots of inner and outer ETDRS ring macular thickness provide objective evidence of this early structural change several years before conventional signs appear. This approach can alert patients and prescribing physicians to potential retinal damage and uses readily available OCT measurements that could be automated by manufacturers for use in comprehensive eye care settings. [ABSTRACT FROM AUTHOR]

Tenecteplase has been compared to alteplase in acute stroke randomized trials, with similar outcomes and safety measures, but higher doses of tenecteplase have been associated with higher hemorrhage rates in some studies. Limited data are available on the safety of tenecteplase outside of clinical trials. We examined the safety measures of intracranial hemorrhage, angioedema, and serious extracranial adverse events in a 21-hospital integrated healthcare system that switched from alteplase (0.9 mg/kg, maximum dose 90 mg) to tenecteplase (0.25 mg/kg, maximum dose 25 mg) for acute ischemic stroke. Among 3,689 subjects, no significant differences were seen between tenecteplase and alteplase in the rate of intracranial hemorrhage (ICH), parenchymal hemorrhage, or volume of parenchymal hemorrhage. Symptomatic hemorrhage (sICH) was not different between the two agents: sICH by NINDS criteria was 2.0 % for alteplase vs 2.3 % for tenecteplase (P = 0.57), and sICH by SITS criteria was 0.8 % vs 1.1 % (P = 0.39). Adjusted logistic regression models also showed no differences between tenecteplase and alteplase: the odds ratio for tenecteplase (vs alteplase) modeling sICH by NINDS criteria was 0.9 (95 % CI 0.33 - 2.46, P = 0.83) and the odds ratio for tenecteplase modeling sICH by SITS criteria was 1.12 (95 % CI 0.25 - 5.07, P = 0.89). Rates of angioedema and serious extracranial adverse events were low and did not differ between tenecteplase and alteplase. Elapsed door-to-needle times showed a small improvement after the switch to tenecteplase (51.8 % treated in under 30 min with tenecteplase vs 43.5 % with alteplase, P < 0.001). : In use outside of clinical trials, complication rates are similar between tenecteplase and alteplase. In the context of a stroke telemedicine program, the rates of hemorrhage observed with either agent were lower than expected based on prior trials and registry data. The more easily prepared tenecteplase was associated with a lower door-to-needle time. [ABSTRACT FROM AUTHOR]

Purpose To compare the accuracy of intraocular lens (IOL) calculation formulas (Barrett Universal II, Haigis, Hoffer Q, Holladay 1, Holladay 2, Olsen, and SRK/T) in the prediction of postoperative refraction using a single optical biometry device. Design Retrospective consecutive case series. Participants A total of 13 301 cataract operations with an AcrySof SN60WF implant and 5200 operations with a SA60AT implant (Alcon Laboratories, Inc., Fort Worth, TX). Methods All patients undergoing cataract surgery between July 1, 2014, and December 31, 2015, with Lenstar 900 optical biometry were eligible. A single eye per patient was included in the final analysis, resulting in a total of 18 501 cases. We compared the performance of each formula with respect to the error in predicted spherical equivalent and evaluated the effect of applying the Wang–Koch (WK) adjustment for eyes with axial length >25.0 mm on 4 of the formulas. Results For the SN60WF, the standard deviation of the prediction error, in order of lowest to highest, was the Barrett Universal II (0.404), Olsen (0.424), Haigis (0.437), Holladay 2 (0.450), Holladay 1 (0.453), SRK/T (0.463), and Hoffer Q (0.473), and the results for the SA60AT were similar. The Barrett formula was significantly better than the other formulas in postoperative refraction prediction ( P < 0.01) for both IOL types. Application of the WK axial length modification generally resulted in a shift from hyperopic to myopic outcomes in long eyes. Conclusions Overall, the Barrett Universal II formula had the lowest prediction error for the 2 IOL models studied. [ABSTRACT FROM AUTHOR]

Purpose To evaluate the association between refractive error and the prevalence of glaucoma by race or ethnicity. Design Cross-sectional study. Participants Kaiser Permanente Northern California Health Plan members with refractive error measured at 35 years of age or older between 2008 and 2014 and with no history of cataract surgery, refractive surgery, or a corneal disorder. Methods We identified 34 040 members with glaucoma or ocular hypertension (OHTN; cases) and 403 398 members without glaucoma (controls). Glaucoma cases were classified as primary angle-closure glaucoma (PACG); 1 of the 4 forms of open-angle glaucoma: primary open-angle glaucoma (POAG), normal-tension glaucoma (NTG), pigmentary glaucoma (PIGM), and pseudoexfoliation glaucoma (PEX); or OHTN. Refractive error, expressed as spherical equivalent (SE), was coded as a continuous trait and also as categories. Logistic regression analyses were used to estimate the association between refractive error and the prevalence of glaucoma overall and in specific racial or ethnic groups. Main Outcome Measures The association between refractive error and glaucoma subtypes evaluated as odds ratios (ORs) with 95% confidence intervals (CIs). Results In controls, the mean SE was −0.59 diopters (D) (standard deviation, 2.62 D). Each 1-D reduction in SE was associated with a 22% decrease in the odds of PACG (OR, 0.78; 95% CI, 0.77–0.80) and with increases in the odds of open-angle glaucoma ranging from 1.23 (95% CI, 1.20–1.26) for PIGM, to 1.07 (95% CI, 1.03–1.11) for PEX, and to 1.05 (95% CI, 1.04–1.06) for OHTN. In addition, we observed a stronger association between myopia and POAG among non-Hispanic whites (OR, 1.12; 95% CI, 1.11–1.13) and NTG among Asians (OR, 1.17; 95% CI, 1.15–1.20) and non-Hispanic whites (OR, 1.19; 95% CI, 1.15–1.22). Conclusions Myopia was associated with an increased prevalence of all forms of open-angle glaucoma and OHTN, whereas hyperopia was associated with a substantially increased prevalence of PACG. Although high myopia is a strong risk factor for glaucoma subtypes, low and moderate myopia also have a significant effect on glaucoma risk. Additionally, there were moderate racial differences in the association of myopia with the risk of POAG and NTG. [ABSTRACT FROM AUTHOR]

Purpose A pericentral pattern of hydroxychloroquine (HCQ) retinopathy recently has been recognized in the United States in patients of Asian heritage. We report on an investigation of this pericentral retinopathy within a Korean population. Design Retrospective, observational study. Participants Patients taking HCQ who were referred to ophthalmology for screening of HCQ retinopathy. Methods The medical records of patients were reviewed, including spectral domain optical coherence tomography, fundus autofluorescence, and visual fields. Main Outcome Measures Frequency of pericentral pattern of HCQ retinopathy and features of progression. Results Among 218 patients referred, 9 (4.1%) were diagnosed with toxicity. Of these, 8 had a predominantly pericentral pattern of retinal change, whereas only 1 had the classic parafoveal distribution of retinal damage. Progression of retinopathy was documented in 3 patients followed more than 12 months while taking HCQ. No progression was seen in 2 patients without retinal pigment epithelial (RPE) damage who were followed for at least 12 months after discontinuation of HCQ. Conclusions We found that a pericentral pattern of HCQ retinopathy was predominant among Korean patients, rather than the traditional (bull's eye) parafoveal pattern of damage. Retinopathy progressed while on the drug, but the progression stopped in patients with toxicity detected before RPE damage. These observations suggest the need for new approaches when screening for HCQ toxicity in Asian patients. [ABSTRACT FROM AUTHOR]

Purpose To describe patterns of hydroxychloroquine retinopathy distinct from the classic parafoveal (bull's eye) maculopathy. Design Retrospective case series. Participants Patients from a large multi-provider group practice and a smaller university referral practice diagnosed with hydroxychloroquine retinopathy. Patients with widespread or “end-stage” retinopathy were excluded. Methods Review of ophthalmic studies (fundus photography, spectral-domain optical coherence tomography, fundus autofluorescence, multifocal electroretinography, visual fields) and classification of retinopathy into 1 of 3 patterns: parafoveal (retinal changes 2°–6° from the fovea), pericentral (retinal changes ≥8° from the fovea), or mixed (retinal changes in both parafoveal and pericentral areas). Main Outcome Measures Relative frequency of different patterns of hydroxychloroquine retinopathy and comparison of risk factors. Results Of 201 total patients (18% Asian) with hydroxychloroquine retinopathy, 153 (76%) had typical parafoveal changes, 24 (12%) also had a zone of pericentral damage, and 24 (12%) had pericentral retinopathy without any parafoveal damage. Pericentral retinopathy alone was seen in 50% of Asian patients but only in 2% of white patients. Patients with the pericentral pattern were taking hydroxychloroquine for a somewhat longer duration (19.5 vs. 15.0 years, P < 0.01) and took a larger cumulative dose (2186 vs. 1813 g, P = 0.02) than patients with the parafoveal pattern, but they were diagnosed at a more severe stage of toxicity. Conclusions Hydroxychloroquine retinopathy does not always develop in a parafoveal (bull's eye) pattern, and a pericentral pattern of damage is especially prevalent among Asian patients. Screening practices may need to be adjusted to recognize pericentral and parafoveal hydroxychloroquine retinopathy. [ABSTRACT FROM AUTHOR]

Purpose: American Academy of Ophthalmology recommendations for screening for hydroxychloroquine (HCQ) retinopathy advise objective measures, such as spectral-domain optical coherence tomography (SD-OCT) and multifocal electroretinography (mfERG) along with visual fields. However, the relative sensitivity and speci-ficity of screening tests have not been fully resolved. We characterize a subset of patients with toxicity who show unusual disparity between fields and SD-OCT and thus have implications for screening practice. Design: Review of charts and clinical data. Participants: Patients at Stanford and Kaiser Permanente who had used HCQ with greater than 1000 g cu-mulative exposure. There were more than 2000 such individuals, among whom 150 had clear evidence of toxicity. Methods: Patients were evaluated by visual fields (10-2 white Swedish Interactive Threshold Algorithm pattern deviation plots), SD-OCT, and sometimes mfERG or fundus autofluorescence. Main Outcome Measures: Relative findings on visual fields in comparison with SD-OCT. Results: There were 11 patients among those with HCQ toxicity who had parafoveal ring scotomas but a normal-appearing SD-OCT. None had a history of macular disease or evidence for any other cause of bull's eye maculopathy. Conversely, all cases with a clear degree of parafoveal damage on SD-OCT showed at least some focal spots of parafoveal field loss Conclusions: Approximately 10% of patients with early HCQ toxicity showed prominent ring scotomas on field testing without obvious SD-OCT abnormality. This should encourage the inclusion of visual fields as a key screening tool, even when SD-OCT (a more specific and objective test) also is performed. The combination of visual fields and SD-OCT gives both sensitivity and specificity while avoiding unnecessary stoppage of the drug. [ABSTRACT FROM AUTHOR]

To evaluate the risk factors for retinal tear (RT) or rhegmatogenous retinal detachment (RRD) associated with acute, symptomatic posterior vitreous detachment (PVD) in a large comprehensive eye care setting. Retrospective cohort study. A total of 8305 adult patients in the Kaiser Permanente Northern California Healthcare System (KPNC) during calendar year 2018 who met inclusion criteria. The KPNC electronic medical record was queried to capture acute, symptomatic PVD events. Each chart was reviewed to confirm diagnoses and capture specific data elements from the patient history and ophthalmic examination. Presence of RT or RRD at initial presentation or within 1 year thereafter. Of 8305 patients who presented with acute PVD symptoms, 448 (5.4%) were diagnosed with RT and 335 (4.0%) were diagnosed with RRD. When considering variables available before examination, blurred vision (odds ratio [OR], 2.7; confidence interval [CI], 2.2–3.3), male sex (OR, 2.1; CI, 1.8–2.5), age < 60 years (OR, 1.8; CI, 1.5–2.1), prior keratorefractive surgery (OR, 1.6; CI, 1.3–2.0), and prior cataract surgery (OR, 1.4; CI, 1.2–1.8) were associated with higher risk of RT or RRD, whereas symptoms of flashes were mildly protective (OR, 0.8; CI, 0.7–0.9). Examination variables associated with a high risk of RT or RRD included vitreous pigment (OR, 57.0; CI, 39.7–81.7), vitreous hemorrhage (OR, 5.9; CI, 4.6–7.5), lattice degeneration (OR, 6.0; CI, 4.7–7.7), and visual acuity worse than 20/40 (OR, 3.0; CI, 2.5–3.7). Late RTs or RRDs occurred in 12.4% of patients who had vitreous hemorrhage, lattice degeneration, or a history of RT or RRD in the fellow eye at initial presentation but only 0.7% of patients without any of these 3 risk factors. Refractive error had an approximately linear relationship with age at presentation of PVD, with myopic patients presenting at a younger age (r = 0.4). This study, based in a comprehensive eye care setting, found the rate of RT and RRD associated with acute PVD to be lower than rates previously reported by retina subspecialty practices. Several patient features strongly predicted the presence of initial and late complications of acute PVD. [ABSTRACT FROM AUTHOR]

To identify genetic variants associated with pigment dispersion syndrome (PDS) and pigmentary glaucoma (PG) in unrelated patients and to further understand the genetic and potentially causal relationships between PDS and associated risk factors. A 2-stage genome-wide association meta-analysis with replication and subsequent in silico analyses including Mendelian randomization. A total of 574 cases with PG or PDS and 52 627 controls of European descent. Genome-wide association analyses were performed in 4 cohorts and meta-analyzed in 3 stages: (1) a discovery meta-analysis was performed in 3 cohorts, (2) replication was performed in the fourth cohort, and (3) all 4 cohorts were meta-analyzed to increase statistical power. Two-sample Mendelian randomization was used to determine whether refractive error and intraocular pressure exert causal effects over PDS. The association of genetic variants with PDS and whether myopia exerts causal effects over PDS. Significant association was present at 2 novel loci for PDS/PG. These loci and follow-up analyses implicate the genes gamma secretase activator protein (GSAP) (lead single nucleotide polymorphism [SNP]: rs9641220, P = 6.0×10-10) and glutamate metabotropic receptor 5 (GRM5) /TYR (lead SNP: rs661177, P = 3.9×10-9) as important factors in disease risk. Mendelian randomization showed significant evidence that negative refractive error (myopia) exerts a direct causal effect over PDS (P = 8.86×10-7). Common SNPs relating to the GSAP and GRM5/TYR genes are associated risk factors for the development of PDS and PG. Although myopia is a known risk factor, this study uses genetic data to demonstrate that myopia is, in part, a cause of PDS and PG. [ABSTRACT FROM AUTHOR]

Background The American Academy of Ophthalmology recommendations on screening for chloroquine (CQ) and hydroxychloroquine (HCQ) retinopathy are revised in light of new information about the prevalence of toxicity, risk factors, fundus distribution, and effectiveness of screening tools. Pattern of Retinopathy Although the locus of toxic damage is parafoveal in many eyes, Asian patients often show an extramacular pattern of damage. Dose We recommend a maximum daily HCQ use of ≤5.0 mg/kg real weight, which correlates better with risk than ideal weight. There are no similar demographic data for CQ, but dose comparisons in older literature suggest using ≤2.3 mg/kg real weight. Risk of Toxicity The risk of toxicity is dependent on daily dose and duration of use. At recommended doses, the risk of toxicity up to 5 years is under 1% and up to 10 years is under 2%, but it rises to almost 20% after 20 years. However, even after 20 years, a patient without toxicity has only a 4% risk of converting in the subsequent year. Major Risk Factors High dose and long duration of use are the most significant risks. Other major factors are concomitant renal disease, or use of tamoxifen. Screening Schedule A baseline fundus examination should be performed to rule out preexisting maculopathy. Begin annual screening after 5 years for patients on acceptable doses and without major risk factors. Screening Tests The primary screening tests are automated visual fields plus spectral-domain optical coherence tomography (SD OCT). These should look beyond the central macula in Asian patients. The multifocal electroretinogram (mfERG) can provide objective corroboration for visual fields, and fundus autofluorescence (FAF) can show damage topographically. Modern screening should detect retinopathy before it is visible in the fundus. Toxicity Retinopathy is not reversible, and there is no present therapy. Recognition at an early stage (before any RPE loss) is important to prevent central visual loss. However, questionable test results should be repeated or validated with additional procedures to avoid unnecessary cessation of valuable medication. Counseling Patients (and prescribing physicians) should be informed about risk of toxicity, proper dose levels, and the importance of regular annual screening. [ABSTRACT FROM AUTHOR]

Purpose Intracameral injection is an effective method for preventing infection, but no controlled study has been published in the United States. Design We conducted an observational, longitudinal cohort study to examine the effect of topical and injected antibiotics on risk of endophthalmitis. Participants We identified 315 246 eligible cataract procedures in 204 515 members of Kaiser Permanente, California, 2005–2012. Methods The study used information from the membership, medical, pharmacy, and surgical records from the electronic health record. Main Outcome Measures The adjusted odds ratio (OR) and 95% confidence interval (CI) for the association of antibiotic prophylaxis (route and agent) with risk of endophthalmitis was estimated using logistic regression analysis. Results We confirmed 215 cases of endophthalmitis (0.07% or 0.7/1000). Posterior capsular rupture was associated with a 3.68-fold increased risk of endophthalmitis (CI, 1.89–7.20). Intracameral antibiotic was more effective than topical agent alone (OR, 0.58; CI, 0.38–0.91). Combining topical gatifloxacin or ofloxacin with intracameral agent was not more effective than using an intracameral agent alone (compared with intracameral only: intracameral plus topical, OR, 1.63; CI, 0.48–5.47). Compared with topical gatifloxacin, prophylaxis using topical aminoglycoside was ineffective (OR, 1.97; CI, 1.17–3.31). Conclusions Surgical complication remains a key risk factor for endophthalmitis. Intracameral antibiotic was more effective for preventing post-cataract extraction endophthalmitis than topical antibiotic alone. Topical antibiotic was not shown to add to the effectiveness of an intracameral regimen. [ABSTRACT FROM AUTHOR]