Journal Highlights NEW FINDINGS from the PEER-REVIEWED LITERATURE

Journal Highlights NEW FINDINGS FROM THE PEER-REVIEWED LITERATURE

Ophthalmology presence of diabetes or hypertension, standalone treatments (each done with Selected by Stephen D. McLeod, MD and use of systemic steroids. For sen- mitomycin C) and noted similar safety sitivity analyses, they shifted the index profiles and failure rates. Selective Serotonin Reuptake date backward 2 years to account for For this study, the authors reviewed Inhibitors and Cataract Risk latency of cataract recording and to medical records to identify adults with November 2017 ensure that the antidepressant exposure glaucoma who underwent either proce- occurred before the cataract. dure at 1 of 4 academic ophthalmology Do the class of antidepressants known Overall, current long-term use of centers located in different countries. as selective serotonin reuptake inhibi- SSRIs (≥ 20 prescriptions [courses of The primary outcome was hazard ratio tors (SSRIs) raise cataract risk? While treatment]) was not associated with (HR) of failure. Failure was defined as recent population-based elevated risk of 2 consecutive readings of intraocular Volume 124 | Number 11 pp. XXXX–XXXX studies from Canada and Volume 124 | Number 11 | November 2017 cataract, and pressure (IOP; < 6 mm Hg with vision Elsevier | ISSN 0161-6420 the United States suggest results for men loss or > 17 mm Hg without medica- that they do, Becker et al. and women were tions, which they defined as “complete quantified the risk of cata- similar. However, success”) at least 1 month after surgery ract among patients exposed among those in despite in-clinic interventions. Second- to SSRIs and found mixed the 40-64 age ary outcomes included IOP thresholds results, with a slight increase group, cataract of 6-14 mm Hg and 6-21 mm Hg, and in risk observed only among OPHTHALMOLOGY risk was slightly the same thresholds allowing for medi- INSERT ADVERT those between the ages of 40 higher for long- cations (defined as “qualified success”). and 64. term SSRI users Of the patients identified, 159 (185 The researchers drew than for nonusers. eyes) received a microstent and 139 November 2017 their study population from Although diabetes (169 eyes) had trabeculectomy. Preop- the U.K.–based Clinical or cardiovascular eratively, those scheduled for micro- PracticeOPHTHA_v124_i11_COVER.indd 1 Research Datalink 21-07-2017 15:47:58 disease increased stent had better visual acuity, were (CPRD) and included 206,931 adults cataract risk, smoking and obesity did younger, and more often were male. with first-time cataract ≥( 40 years of not. No increase in cataract risk was Other baseline characteristics were age) and an equal number of cata- found for patients who used a single comparable. ract-free controls matched for age, type of SSRI exclusively. For the primary outcome threshold sex, date of cataract recording (index of 6-17 mm Hg, adjusted HRs of failure date), and number of prior years in Microstent or Trabeculectomy: for microstent relative to trabeculec- the CPRD. The mean age at index date Comparing Efficacy, Safety, and tomy were 1.2 for complete success was 73.7 years. Those with a previous Risk of Failure and 1.3 for qualified success. Times to diagnosis of glaucoma were excluded November 2017 25% failure were 11.2 and 10.6 months from sensitivity analyses. for complete success and 30.3 and 33.3 The number of prescriptions for Implanted ab interno gelatin micro- months for qualified success, respec- SSRIs and other antidepressant drugs stents are perceived as safer and less in- tively. White race was linked to lower was noted, as was the exclusive use of a vasive than trabeculectomy for treating risk of failure (adjusted HR, 0.49; more single SSRI. The researchers performed progressive glaucoma, but comparison pronounced with trabeculectomy), and logistic regression analyses, adjusting studies are lacking. Schlenker et al. diabetes was associated with higher fail- for body mass index, smoking status, conducted a retrospective study of the ure risk (adjusted HR, 4.21).

EYENET MAGAZINE • 33 Overall, microstent and trabeculec- 1A 1B tomy recipients underwent 114 and 165 postoperative interventions, respectively, and 43% and 31% underwent needling. Fifty percent of those with trabeculec- tomy had laser suture lysis. There were 22 complications with microstent and 30 with trabeculectomy. Most were transient. Although these findings indicate 2A 2B similar rates of complete and qualified success, the authors urged clinicians to weigh the pitfalls of each procedure, in- cluding the potential for needling and reoperation with microstent and the greater likelihood of interventions and complications after trabeculectomy. (Also see related commentary by Dale K. LHON OUTCOMES. Two patients experienced asymptomatic transient mild anterior Heuer, MD, in the same issue.) uveitis. The eye of a patient treated with low-dose gene therapy (1A) shows fine keratic precipitates (1B). Keratic precipitates in a second patient who was treated Gene Therapy for Leber with medium-dose gene therapy (2A) resolved 1 month later (2B). Hereditary Optic Neuropathy November 2017 inclusion limited to those who would Guy et al. expanded their research on have qualified for the gene therapy at Ophthalmology Retina Selected by Andrew P. Schachat, MD gene therapy for Leber hereditary optic baseline. The worse eye of natural his- neuropathy (LHON) and found that tory patients served as a surrogate for Decreased Fundus Autofluo- their collective results affirm the bene- treated eyes in the current study; better rescence and Visual Acuity in fits of low and moderate doses. eyes served as fellow eyes. Stargardt Disease In this open-label trial, 9 patients For groups 1 and 2 combined, the November/December 2017 with visual loss and mutated G11778A average improvement over 12 months mitochondrial DNA received a unilat- was 0.24 logMAR in treated eyes and Kong et al. set out to investigate the eral single-dose intravitreal injection of 0.09 logMAR in fellow eyes. The dif- association between visual acuity (VA) corrected DNA borne by the adenoas- ference in improvement between study and areas of decreased fundus auto­ sociated vector AAV2(Y444,500,730F)- and fellow eyes was greater in group 2 fluorescence (AF) in patients with P1ND4v2, which had also been admin­ than in the natural history cohort at recent-onset Stargardt disease. They istered previously to 5 other patients. month 12 (0.53 vs. 0.21 logMAR; found a small rate of VA loss per year, Six of the 14 patients had bilateral p = .053) and month 18 (0.96 vs. 0.17 dependent on the level of VA at first visual loss lasting > 12 months (group logMAR; p < .001). visit and the location of lesion growth 1), 6 had bilateral loss for < 12 months The average thickness of the tem- and not significantly associated with (group 2), and 2 had unilateral loss poral retinal nerve fiber layer (RNFL) the rate of increase in areas of de- (group 3). was 54 µm before injection and 55 µm creased AF. Eight patients received the low dose at month 12. The respective values for For this study, the researchers evalu- (5 × e9 vg), and 6 received the medium fellow eyes were 56 µm and 50 µm. ated 64 patients (124 eyes) drawn from dose (2.46 × e10 vg). Nine patients had Esti­mating-equation analysis showed the ProgStar (Progression of atrophy follow-up for ≥ 12 months. that PERG amplitudes worsened more secondary to Stargardt disease) study. Testing included visual acuity (VA), in treated eyes. No between-eye differ­ All were ≥ 6 years of age (median, 22.5 visual field, optical coherence tomog- ences were detected by other visual years) and had experienced symptom raphy, and pattern electroretinogra- function measures. Two patients exhib- onset ≤ 2 years before the first study phy (PERG). Generalized estimating ited uveitis, which was asymptomatic visit. equations were used in longitudinal and resolved (Figs. 1A-2B). VA was measured as best-corrected analyses. The main outcome was In conclusion, low and medium dos- or presenting VA; more than half the change in VA. es of allotopic gene therapy appear safe eyes had a VA worse than 20/70 at Because the study was not random­ for treating LHON and do not damage baseline, and 14.5% were > 20/200. ized or controlled, results were com- the temporal RNFL. These findings In addition, 94% already had areas of Ophthalmology pared with data from the authors’ warrant testing of higher doses. decreased AF (DAF) in their images.

previous natural history cohort, with —Summaries by Lynda Seminara The overall VA change rate was @ 2017

34 • NOVEMBER 2017 0.054 per year; faster rates of loss were and severe visual field (VF) loss. services provided. Codes were used to observed in patients who were 20/30 This prospective cross-sectional categorize each service as a procedure, to 20/70 at baseline as well as in those validation study was conducted at drug, or office visit. The data set was who were younger when symptoms Tilganga Institute of Ophthalmology in limited to ophthalmologists in office or first occurred. While the rate of VA loss Nepal. Screening tests were performed ambulatory surgical settings; optome- was not significantly associated with using a calibrated iPad 2 containing trists were excluded. the rate of increase in areas of definite- the Visual Fields Easy (VFE) app. Of Ophthalmology patients represented ly decreased AF (DDAF), questionably 411 eyes evaluated (206 subjects), 183 3.7% and 3.6% of Medicare benefi- decreased AF (QDAF), or DAF, it was had glaucoma, 18 had diabetic reti- ciaries in 2012 and 2013, respectively. significantly associated with DAF in the nopathy, and 210 were normal. Results The mean age was 75 years; 61% were fovea at baseline. were compared with those obtained female. Aggregate ophthalmology —Summary by Jean Shaw by a Humphrey Field Analyzer for 373 payments totaled $5.6 billion in 2012 of these eyes (glaucoma, 160; diabetic and $5.8 billion in 2013, for an increase American Journal of retinopathy, 15; normal, 198). of 3.6%. Although the quantity of Ophthalmology The VFE iPad app was able to detect reimbursed ophthalmic services rose Selected by Richard K. Parrish II, MD most VF deficits of moderate loss (mean 2% from 2012 to 2013, the mean dollar deviation [MD] of –6 to –12 dB) and amount per service decreased by 5.4%. iPad App Detects VF Loss advanced loss (MD worse than –12 According to gross reimbursements, November 2017 dB). It was not as sensitive for detecting 5 services accounted for 85% of pay- early loss (MD better than –6 dB), due ments to ophthalmologists in 2013, an Many cases of glaucoma are undetected,­ mostly to the high rate of false-positive increase of 11% from 2012. Cataract particularly in developing nations. Cost- responses. The average time to perform surgery topped the list, followed closely effective practical methods are needed the VFE test on each eye was 3 minutes, by injection of anti-VEGF drugs. for detecting glaucoma, diabetic reti- 18 seconds (standard deviation, 16.88 Drug-related reimbursement nopathy, and other vision-threatening seconds). accounted for 32.8% of Medicare conditions. Johnson et al. tested the The authors concluded that the payments ($1.9 billion) to ophthal- accuracy and efficiency of a free iPad VFE iPad app is a portable, quick, and mologists in 2013; ranibizumab and app for suprathreshold perimetric effective method to identify moderate aflibercept represented 95% of these screening. The tool proved fast and and advanced VF loss. Improvements payments. The only specialty that re- accurate for detecting both moderate are underway to enhance performance, ceived higher reimbursement for drugs reduce test time, monitor head and eye was hematology-oncology. Overall, the movement, and eliminate the need to mean reimbursement per ophthalmol- MORE AT touch the screen. ogist was higher for procedures than THE MEETING for drugs or office visits. Ophthalmology and Medicare Reimbursement to The authors concluded that, although Ophthalmology Retina Ophthalmologists Medicare disbursements for drugs are Meet and Greet. Authors November 2017 high for ophthalmology as a specialty, and peer reviewers are this is not surprising given the growing invited to meet members of the In a recent public report on Medicare demand for anti-VEGF agents as the journals’ editorial review boards. Part B spending for 2012 and 2013, population ages. In addition, they said, When: Sunday, Nov. 12, 1:00-3:00 ophthalmologists (who account for 2% findings should be interpreted with p.m. Where: Academy Resource of the physician workforce) were iden- caution because data sources did not Center, Hall G, Booth 3140. Ac- tified as having a disproportionate share include either Medicare members with cess: Free. of disbursements (7.7% in 2013). Han private insurance or patients on Medi-­ Ophthalmology Retina et al. reviewed data for the same period caid. —Summaries by Lynda Seminara Launch Celebration. If you are and determined that, unlike trends an early subscriber to—or have noted in other specialties, a substantial JAMA Ophthalmology been published in—Ophthalmol- number of ophthalmology reimburse- Selected by Neil M. Bressler, MD, and ogy Retina, you are invited to ments were related to medication use, Deputy Editors meet editor-in-chief Andrew primarily injections of anti–vascular P. Schachat, MD, and the edito- endothelial growth factor (VEGF) drugs. Retinal Emboli: Prevalence and rial board. Refreshments will be For this retrospective cross-sectional Systemic Associations served. When: Monday, Nov. 13, study, the authors reviewed Medicare October 2017 10:00-11:00 a.m. Where: Museum Physician and Other Supplier data (both of Vision, Hall G, Booth 3047. aggregate and private use) to determine Population-based data on retinal emboli Access: By invitation. ophthalmic beneficiary demographics, in Asia are limited. In the Singapore Medicare Part B payments, and medical Epidemiology of Eye Disease Study,

EYENET MAGAZINE • 35 Cheung et al. examined prevalence No Relationship Between between OSA presence or severity and and risk factors among a large group Eyelid Laxity and Obstructive markers of laxity or ocular surface dis- of Chinese, Malay, and Indian patients. Sleep Apnea ease. Findings of their subset analysis They found that retinal emboli were October 2017 suggest that earlier studies may have most common among the Indian been hampered by confounding vari- individuals and were associated with Although studies have indicated a ables or the techniques used to deter- chronic kidney disease as well as classic correlation between floppy eyelid mine eyelid laxity. cardiovascular factors. syndrome and obstructive sleep apnea This cross-sectional study included (OSA), the diagnostic criteria for eyelid Incidence of Strabismus in a 9,978 patients (40-80 years of age) with laxity often are vague and subjective. Danish Pediatric Population gradable retinal photographs. Of these, Fox et al. employed quantitative mark- October 2017 88 exhibited retinal emboli, which were ers to assess eyelid laxity and found no identified using a standardized pro- correlation between OSA and floppy Population-based research on the tocol. Age-standardized prevalence of eyelid syndrome. incidence of strabismus is limited. retinal emboli was calculated from the For this cross-sectional observation Torp-Pedersen et al. examined data for 2010 Singapore adult population. In- study, the researchers evaluated 201 young Danish children (≤ 7 years of terviews, lab tests, and comprehensive patients (402 eyes; mean age, 53 years), age) and attained results comparable systemic and ophthalmic exams were all of whom underwent overnight to those of smaller European and U.S. performed to determine risk factors poly­somnography at a sleep center in studies, but the ratio of esotropia to associated with retinal emboli. the United States. Eyelid laxity and exotropia was higher in their study. The overall person-specific, age- ocular surface disease were evaluated The authors reviewed records for standardized prevalence of retinal through detailed bedside ophthalmo- 96,842 children enrolled in the Dan- emboli was 0.75%. Prevalence rates in logic examination, and severity scores ish National Birth Cohort. Primary the Indian, Chinese, and Malay cohorts for these markers were assigned to each outcomes were age-specific incidence were 0.98%, 0.73%, and 0.44%, respec- eye. Bedside exams entailed measur- of strabismus, cumulative incidence of tively. According to multivariable-ad- ing eyelid laxity (including horizontal strabismus, and median age at detec- justed analysis, common risk factors for eyelid distraction, upper eyelid trac- tion (overall and by subtype). retinal emboli were older age, Indian tion, and presence of eyelash ptosis), All told, the researchers identified ethnicity, hypertension, chronic kidney determining ocular surface disease 1,309 cases of strabismus. The overall disease, and history of stroke. (including palpebral conjunctival reac- cumulative incidence of strabismus Elevated creatinine levels and tion), and performing other objective was 2.56% at age 7, and it was similar low glomerular filtration rates were assessments. for boys and girls. The most common consistently linked to retinal emboli, The presence and severity of OSA subtypes identified were congenital independent of age, smoking status, were established from polysomno- esotropia (16.5%, n = 216), fully accom­ concomitant hypertension, and other graphic findings. The initial correlation modative esotropia (13.5%, n = 177), risk factors. Stratified analyses showed between OSA and ocular surface and partially accommodative esotropia a similar correlation between retinal eyelid markers was calculated from bi- (19.3%, n = 252), and exotropia (13.8%, emboli and reduced renal function, variate linear regression analysis. Asso- n = 181). The ratio of esotropia to ex- even for participants without hyperten- ciations between ocular symptoms were otropia was 5.4:1, which is higher than sion or diabetes. The odds of develop- obtained through bivariate ordered that observed in smaller studies. Other ing chronic kidney disease were twice logistic regression. Adjustments were differences from previous findings were as great among individuals with retinal made for known associations between a lower incidence of central nerve sys- emboli. OSA and sex, age, body mass index, and tem–associated strabismus and a great- Of note, some of these relationships concomitant medical conditions. er incidence of congenital esotropia. had not been identified in previous After adjustments, no association Age-specific incidence curves for population-based studies. was observed between OSA severity congenital esotropia, fully accom- The authors concluded that the and eyelid laxity score or ocular surface modative esotropia, partially accom- presence of retinal emboli may signal score. Subset analyses showed a correla- modative esotropia, and all exotropia vascular embolic damage to the brain tion between male gender and higher suggested that the various subtypes as well as the kidneys. If their findings ocular surface score. Older age and have different age-specific incidence are confirmed by longitudinal studies, the presence of diabetes were linked patterns (p < .001 for all pairwise com- it would be prudent to ensure that to greater eyelid laxity. Only 1 patient parisons of curves). The median age at patients with retinal emboli receive exhibited classic signs of floppy eyelid detection of these 4 common subtypes both a renal evaluation and a cardio- syndrome. was 0, 32.0, 26.1, and 16.6 months, vascular assessment. (Also see related The authors concluded that, accord­ respectively. Gender differences, which commentary by Robert N. Frank, MD, in ing to their method for measuring eye­lid were nominal, were observed for only the same issue.) laxity, no significant relationship exists 3 subtypes (accommodative esotro-

36 • NOVEMBER 2017 pia; microesotropia; and intermittent and a software-derived image-quality As the opioid crisis continues in esotropia). (Also see related commentary score of at least 60 were necessary to the United States, clinicians should by Scott R. Lambert, MD, in the same obtain good (ICC > 0.6) or excellent maintain a high degree of suspicion for issue.) —Summaries by Lynda Seminara (ICC > 0.75) repeatability. Variations in EFE, the authors noted, as patients are centration and image tilt did not affect ambulatory at presentation and may OTHER JOURNALS measurement repeatability for either not have systemic signs of infection. Selected by Deepak P. Edward, MD plexus. —Summaries by Lynda Seminara

OCT-A Measurement of Retinal Fallout From the Opioid Crisis: Global Look at Visual Impairment Vessel Density: Key Factors IV Drug Abuse and Endogenous Lancet Global Health Influencing Repeatability Fungal Endophthalmitis 2017;5(9):e888-e897 British Journal of Ophthalmology JAMA Ophthalmology Published online Aug. 16, 2017 2017;135:534-540 Bourne et al. set out to provide world- wide estimates, trends, and projections Optical coherence tomography angi- Abuse of intravenous (IV) drugs is of vision impairment and visual loss. ography (OCT-A) may permit rapid a risk factor for endogenous fungal They found mixed results: On one hand, quantification of retinal capillary endophthalmitis (EFE), a severe vision- the age-standardized prevalence of plexus density in various disease states. threatening intraocular infection. visual impairment and loss continue Although studies have indicated that Tirpack et al. updated the character- to decline. On the other, however, the OCT-A has potential for excellent istics, management, and visual out- overall growth in population—and the reproducibility and repeatability, meth- comes among patients with EFE and aging of that population—is contrib- ods of appraising scan quality have not found that this infection signals severe uting to a substantial increase in the been clearly defined.Fenner et al. set end-organ damage and poor visual number of people affected. out to identify key factors affecting the outcomes. For this meta-analysis, the research- repeatability of OCT-A measurements For this study, the authors reviewed ers updated an earlier report, for a total and noted the importance of ensuring records for all patients with EFE referred of 288 population-based studies con- visibility of fine vasculature while mini- to New England Eye Center at Tufts tributing data from 98 countries. Of mizing motion artifact. Medical Center from May 2014 to May the 7.33 billion people alive in 2015, an For this study, the researchers 2016. Patients with a history of IV drug estimated 36 million (crude prevalence obtained OCT-A images of 44 healthy abuse and clinical evidence or culture 0.48%) were blind (defined as visual eyes (44 subjects; mean age, 70 years) proof of fungal endophthalmitis were acuity [VA] worse than 20/400), 216 during 2 separate clinic visits. Each eye included. Patient data were collected, million had moderately and severe im- was examined using the Topcon DRI including demographics, comorbidi- paired VA (between 20/400 and 20/60), OCT Triton imaging system. Parafoveal ties, presenting symptoms, vitreoretinal and 188 million had mildly impaired vessel density within a 1.5-mm radius findings, treatment regimens, culture VA (between 20/60 and 20/40). centered over the fovea was determined results, and visual acuity (before and For the first time, there was enough with the built-in tool for assessing after treatment). information on presbyopia for the superficial and deep retinal plexuses. Ten patients with EFE related to researchers to complete a meaningful Repeatability of vessel density was IV drug abuse were identified during analysis of the condition. They estimate ascertained by intraclass correlation the study window period. Their mean that 666.7 million people ≥ 50 years (ICC) and mean variation. Several im- age was 34 years (range, 24-60 years), of age and 1.09 billion people ≥ 35 age-quality parameters were evaluated and 50% were female. Presenting visual years of age are affected by uncorrected to determine their influence on the acuity ranged from 20/25 to hand mo- presbyopia. repeatability of vessel density measure- tion. All patients were ambulatory at Most of those who had the poorest ments in each capillary plexus. presentation, and 90% had isolated VA resided in south Asia, east Asia, and The repeatability of measurements ocular symptoms but no systemic sign Southeast Asia; and the age-standard- was better for the superficial plexus, of infection. The most common pre- ized prevalence of blindness was high- a finding that has been reported by senting symptoms were floaters (n = 8), est in south Asia, western sub-Saharan other investigators. For the superficial reduced vision (n = 6), and pain (n = 5). Africa, and eastern sub-Saharan Africa. plexus, mean parafoveal vessel density Initial treatment included systemic In addition, more women than men measurements for the first and second antifungals (all patients) and intra­ were visually impaired. visits were 53.3 ± 11.1 and 53.3 ± 10.3, vitreal antifungals (9 eyes). Pars plana The findings highlight the need to respectively; for the deep plexus, those vitrectomy was performed in 5 patients scale up current efforts to improve measurements were 27.3 ± 8.59 and because of worsening vitritis. The most vision, the researchers said, given the 27.0 ± 8.78, respectively. According commonly isolated pathogen was Can- impact that visual acuity has on quality to ICC analyses, clear visibility of fine dida albicans. After treatment, visual of life and economic security. vessels, absence of motion artifact, acuity ranged from 20/40 to 20/300. —Summary by Jean Shaw

EYENET MAGAZINE • 37