Category: Peer-reviewed

Peripheral Autofluorescence and Clinical Findings in Neovascular and Non-neovascular Age-related Macular Degeneration – Corrected Proof

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Purpose:
To characterize peripheral fundus autofluorescence (FAF) abnormalities in patients with age-related macular degeneration (AMD), correlate these with clinical findings, and identify risk factors associated with these FAF abnormalities.

Design:
Clinic-based, cross-sectional study.

Participants:
A total of 119 consecutive patients: 100 patients with AMD (200 eyes) and 19 patients without AMD (38 eyes).

Methods:
In a prospective study performed at the Doheny Eye Institute, University of Southern California, widefield 200-degree FAF and color images were obtained by the Optos 200Tx Ultra-Widefield device (Optos, Dunfermline, Scotland) using a standardized imaging protocol. The FAF images were captured centered on the fovea, and additional images were captured after steering the field of view inferiorly and superiorly. All FAF and color images were graded independently by 2 masked ophthalmologists with respect to the presence, location, extent, and type of peripheral (defined as outside the central 30 degrees) FAF abnormality.

Main Outcome Measures:
Presence and type of peripheral FAF abnormalities.

Results:
Peripheral FAF abnormalities were evident in 164 eyes (68.9%), with several distinct FAF patterns identified: granular (46.2%), mottled (34.0%), and nummular (18.1%). A 90% concordance of FAF patterns was observed between both eyes. Abnormal FAF occurred more frequently in neovascular compared with non-neovascular AMD or normal eyes (86% vs. 72.8% vs. 18.4%, respectively, P<0.001). Significant risk factors for peripheral FAF abnormalities were AMD type (neovascular AMD odds ratio [OR], 12.7 and non-neovascular AMD OR, 6.2 compared with normal eyes, P<0.001), older age (OR, 6.5; 95% confidence interval [CI], 2.4–17.8; P<0.001 for the oldest quartile compared with the youngest), and female sex (OR, 4.1; 95% CI, 1.9–8.9; P<0.001). Clinical features on color photography were detected in 174 eyes (73.1%): peripheral drusen (51.7%), retinal pigment epithelium (RPE) depigmentation (34.9%), RPE hyperpigmentation (branching reticular pigmentation) (22.7%), and atrophic patches (16.8%). There was a high correlation between specific FAF and clinical findings: granular FAF with peripheral drusen (P<0.001) and mottled FAF with RPE depigmentation (P<0.001).

Conclusions:
Several distinct patterns of peripheral FAF abnormalities were observed in 68.9% of patients, with AMD type, female sex, and age being independent risk factors. The peripheral FAF patterns correlate strongly with specific clinical features seen in eyes with AMD.

Financial Disclosure(s):
Proprietary or commercial disclosure may be found after the references.

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One-Year Strabismus Outcomes in the Infant Aphakia Treatment Study – Corrected Proof

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Objective:
To evaluate the characteristics of strabismus in infants who underwent cataract surgery with and without intraocular lens (IOL) implantation.

Design:
Secondary outcome analysis in a prospective, randomized clinical trial.

Participants:
The Infant Aphakia Treatment Study is a randomized, multicenter (n = 12), clinical trial comparing treatment of aphakia with a primary IOL or contact lens in 114 infants with a unilateral congenital cataract.

Intervention:
Infants underwent cataract surgery with or without placement of an IOL.

Main Outcome Measures:
The proportion of patients in whom strabismus developed during the first 12 months of follow-up was calculated using the life-table method and was compared across treatment groups and age strata using a log-rank test.

Results:
Strabismus developed within the first 12 months of follow-up in 38 pseudophakic infants (life-table estimate, 66.7%) and 42 infants (life-table estimate, 74.5%) treated with contact lenses (P = 0.59). The younger cohort (<49 days) at the time of surgery demonstrated less strabismus (29 of 50; life-table estimate, 58.0%) than the older cohort (≥49 days; 51 of 64; life-table estimate, 80.0%; P<0.01).

Conclusions:
Intraocular lens placement does not prevent the early development of strabismus after congenital cataract surgery. However, strabismus was less likely to develop in infants whose cataract was removed at an earlier age.

Financial Disclosure(s):
The author(s) have no proprietary or commercial interest in any materials discussed in this article.

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Comparison of Treatment Regimens for Cytomegalovirus Retinitis in Patients with AIDS in the Era of Highly Active Antiretroviral Therapy – Corrected Proof

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Purpose:
To describe the outcomes of different treatment approaches for cytomegalovirus (CMV) retinitis in the era of highly active antiretroviral therapy (HAART).

Design:
Prospective cohort study, the Longitudinal Study of the Ocular Complications of AIDS.

Participants:
A total of 250 patients with CMV retinitis and a CD4+ T-cell count <100 cells/μl (n = 221) at enrollment or incident retinitis (n = 29) during cohort follow-up.

Methods:
The effects of systemic therapy (vs. intraocular therapy only) on systemic outcomes and the effect of intraocular therapies (ganciclovir implants, intravitreal injections) on ocular outcomes were evaluated.

Main Outcome Measures:
Mortality, CMV dissemination, retinitis progression, and treatment side effects.

Results:
Regimens containing systemic anti-CMV therapy were associated with a 50% reduction in mortality (adjusted hazard ratio [HR], 0.5; 95% confidence interval [CI], 0.3–0.7; P = 0.006), a 90% reduction in new visceral CMV disease (adjusted HR, 0.1; 95% CI, 0.04–0.4; P = 0.004), and among those with unilateral CMV retinitis at presentation, an 80% reduction in second eye disease (adjusted HR, 0.2; 95% CI, 0.1–0.5; P = 0.0005) when compared with those using only intraocular therapy (implants or injections). Compared with systemic treatment only, regimens containing intravitreal injections had greater rates of retinitis progression (adjusted HR, 3.4; P = 0.004) and greater visual field loss (for loss of one half of the normal field, adjusted HR, 5.5; P < 0.01). Intravitreal implants were not significantly better than systemic therapy (adjusted HR for progression, 0.5; P = 0.26; adjusted HR for loss of one half of the visual field, 0.5; P = 0.45), but the sample size was small. Hematologic and renal side effect rates were similar between those groups with and without systemic anti-CMV therapy. The rate of endophthalmitis was 0.017 per eye-year (EY) (95% CI, 0.006–0.05) among those treated with intravitreal injections and 0.01 per EY (95% CI, 0.002–0.04) among those treated with an implant.

Conclusions:
In the HAART era, systemic anti-CMV therapy, while there is immune compromise, seems to provide benefits in terms of longer survival and decreased CMV dissemination.

Financial Disclosure(s):
Proprietary or commercial disclosure may be found after the references.

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Body Stature Growth Trajectories during Childhood and the Development of Myopia – Corrected Proof

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Purpose:
Stature at a particular age can be considered the cumulative result of growth during a number of preceding growth trajectory periods. We investigated whether height and weight growth trajectories from birth to age 10 years were related to refractive error at ages 11 and 15 years, and eye size at age 15 years.

Design:
Prospective analysis in a birth cohort.

Participants:
Children participating in the Avon Longitudinal Study of Parents and Children (ALSPAC) U.K. birth cohort (minimum N = 2676).

Methods:
Growth trajectories between birth and 10 years were modeled from a series of height and weight measurements (N = 6815). Refractive error was assessed by noncycloplegic autorefraction at ages 11 and 15 years (minimum N = 4737). Axial length (AXL) and radius of corneal curvature were measured with an IOLMaster (Carl Zeiss Meditec, Welwyn Garden City, U.K.) at age 15 years (minimum N = 2676). Growth trajectories and an allelic score for 180 genetic variants associated with adult height were tested for association with refractive error and eye size.

Main Outcome Measures:
Noncycloplegic autorefraction at ages 11 and 15 years, and AXL and corneal curvature at age 15 years.

Results:
Height growth trajectory during the linear phase between 2.5 and 10 years was negatively associated with refractive error at 11 and 15 years (P<0.001), but explained <0.5% of intersubject variation. Height and weight growth trajectories, especially shortly after birth, were positively associated with AXL and corneal curvature (P<0.001), predicting 1% to 5% of trait variation. Height growth after 2.5 years was not associated with corneal curvature, whereas the association with AXL continued up to 10 years. The height allelic score was associated with corneal curvature (P = 0.03) but not with refractive error or AXL.

Conclusions:
Up to the age of 10 years, shared growth mechanisms contribute to scaling of eye and body size but minimally to the development of myopia.

Financial Disclosure(s):
The author(s) have no proprietary or commercial interest in any materials discussed in this article.

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Predictive Value in Retinal Vein Occlusions of Early Versus Late or Incomplete Ranibizumab Response Defined by Optical Coherence Tomography – Corrected Proof

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Purpose:
To determine if optical coherence tomography (OCT) at baseline or month 3 in the Treatment of Macular Edema following Branch Retinal Vein Occlusion: Evaluation of Efficacy and Safety (BRAVO) and Treatment of Macular Edema following Central Retinal Vein Occlusion: Evaluation of Efficacy and Safety (CRUISE) studies provides information that predicts visual outcome.

Design:
Post hoc analysis from 2 prospective, randomized, controlled clinical trials.

Participants:
Three hundred ninety-seven patients from the BRAVO study and 392 patients from the CRUISE study.

Methods:
Time-domain OCT imaging data were analyzed.

Main Outcome Measures:
Mean change from baseline best-corrected visual acuity (BCVA) letter score at month 6 and month 12.

Results:
Among ranibizumab-treated patients, 71.2% (0.3 mg) and 78.5% (0.5 mg) in the CRUISE study and 79.1% (0.3 mg) and 84.7% (0.5 mg) in the BRAVO study had central foveal thickness (CFT) of 250 μm or less at month 3 and therefore were categorized as early ranibizumab responders. Early ranibizumab responders had excellent visual outcomes regardless of ranibizumab dose; mean improvement in BCVA letter score at 6 and 12 months was 15.0 to 16.5 (central retinal vein occlusion [CRVO]) and 17.4 to 19.1 (branch retinal vein occlusion [BRVO]). Late or incomplete ranibizumab responders with CRVO (CFT >250 μm at month 3) did not fare as well as early responders if they were treated with 0.3 mg ranibizumab (month 6, P = 0.012). At month 6, compared with ranibizumab-treated CRVO patients with resolved cystoid macular edema (CME) at month 3, those with persistent CME did worse, on average, and significantly so for 0.5 mg (13.1 vs. 18.6; P = 0.027). At baseline, subretinal fluid (SRF) was present in 57% of patients with CRVO and in 45% of patients with BRVO; its presence did not portend a poor outcome in patients treated with ranibizumab for whom SRF was eliminated in almost all by month 3.

Conclusions:
At month 3 of ranibizumab treatment, OCT images provide predictive information for patients with CRVO, but not for those with BRVO. Visual outcome at months 6 and 12 was reduced in 0.5 mg ranibizumab-treated patients with CRVO who had persistent CME at month 3. It also was reduced in CRVO for those with CFT of more than 250 μm at month 3 who were treated with 0.3 mg ranibizumab. The findings suggest that late or incomplete responders may need careful follow-up.

Financial Disclosure(s):
Proprietary or commercial disclosure may be found after the references.

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Changes in Ocular Flora in Eyes Exposed to Ophthalmic Antibiotics – Corrected Proof

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Purpose:
To determine changes in ocular flora in individuals repeatedly exposed to topical macrolide or fluoroquinolone antibiotics.

Design:
Prospective, controlled, longitudinal study with 1-year follow-up.

Participants:
Forty-eight eyes of 24 patients undergoing serial unilateral intravitreal injection for choroidal neovascularization.

Methods:
Patients received 4 consecutive monthly unilateral intravitreal injections and were then treated as needed. Each patient was randomized to 1 of 4 antibiotics (azithromycin 1%, gatifloxacin 0.3%, moxifloxacin 0.5%, ofloxacin 0.3%) and used only their assigned antibiotic for 4 days after each injection. Conjunctival cultures of the treated eye and untreated fellow eye (control) were taken at baseline and before each injection. All bacterial isolates were tested for antibiotic susceptibility to 16 different antibiotics using the Kirby–Bauer disc diffusion technique.

Main Outcome Measures:
Changes in bacteria composition of the conjunctiva over time.

Results:
In azithromycin-treated eyes, Staphylococcus epidermidis and Staphylococcus aureus accounted for 54.5% and 18.2% of cultured isolates, respectively, at baseline and 90.9% (P<0.01) and 4.5% (P<0.01), respectively, after azithromycin exposure. In fluoroquinolone-treated eyes, 45.7% and 6.5% of cultured isolates at baseline were S epidermidis and S aureus, respectively, but these percentages increased to 63.4% (P<0.03) and 13% (P = 0.24), respectively, after fluoroquinolone exposure. In contrast, the percentage of gram-negative species decreased from 8.7% at baseline to 1.6% (P<0.05) in fluoroquinolone-treated eyes. The percentage of S epidermidis isolated from azithromycin-treated eyes was significantly greater when compared with fellow control eyes (P<0.01) or fluoroquinolone-treated eyes (P<0.01).

Conclusions:
The percentage of S epidermidis isolated from the conjunctival surface significantly increases after repeated exposure to azithromycin and to a lesser degree fluoroquinolone antibiotics at the expense of other commensal flora.

Financial Disclosure(s):
The author(s) have no proprietary or commercial interest in any materials discussed in this article.

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Oral Docosahexaenoic Acid in the Prevention of Exudative Age-Related Macular Degeneration: The Nutritional AMD Treatment 2 Study

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Objective: To evaluate the efficacy of docosahexaenoic acid (DHA)–enriched oral supplementation in preventing exudative age-related macular degeneration (AMD).Design: The Nutritional AMD Treatment 2 study was a randomized, placebo-controlled, double-blind, parallel, comparative study.Participants: Two hundred sixty-three patients 55 years of age or older and younger than 85 years with early lesions of age-related maculopathy and visual acuity better than 0.4 logarithm of minimum angle of resolution units in the study eye and neovascular AMD in the fellow eye.Methods: Patients were assigned randomly to receive either 840 mg/day DHA and 270 mg/day eicosapentaenoic acid (EPA) from fish oil capsules or the placebo (olive oil capsules) for 3 years.Main Outcome Measures: The primary outcome measure was time to occurrence of choroidal neovascularization (CNV) in the study eye. Secondary outcome measures in the study eye were: incidence of CNV developing in patients, changes in visual acuity, occurrence and progression of drusen, and changes in EPA plus DHA level in red blood cell membrane (RBCM).Results: Time to occurrence and incidence of CNV in the study eye were not significantly different between the DHA group (19.5±10.9 months and 28.4%, respectively) and the placebo group (18.7±10.6 months and 25.6%, respectively). In the DHA group, EPA plus DHA levels increased significantly in RBCM (+70%; P<0.001), suggesting that DHA easily penetrated cells, but this occurred unexpectedly also in the placebo group (+9%; P = 0.007). In the DHA-allocated group, patients steadily achieving the highest tertile of EPA plus DHA levels in RBCM had significantly lower risk (−68%; P = 0.047; hazard ratio, 0.32; 95% confidence interval, 0.10–0.99) of CNV developing over 3 years. No marked changes from baseline in best-corrected visual acuity, drusen progression, or geographic atrophy in the study eye were observed throughout the study in either group.Conclusions: In patients with unilateral exudative AMD, 3 years of oral DHA-enriched supplementation had the same effect on CNV incidence in the second eye as did the placebo. However, RBCM fatty acid measurements revealed that CNV incidence was significantly reduced in DHA-supplemented patients showing a steadily high EPA plus DHA index over 3 years.Financial Disclosure(s): Proprietary or commercial disclosure may be found after the references.

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The Effect of Prior Trabeculectomy on Refractive Outcomes of Cataract Surgery – Corrected Proof

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Purpose: To examine surgical and refractive outcomes of phacoemulsification with intraocular lens (IOL) implant in eyes with prior trabeculectomy.Design: Retrospective observational case-control study.Methods: The study compared eyes that underwent phacoemulsification with IOL implant at least 3 months post-trabeculectomy (n = 77) with eyes with either medically controlled glaucoma (n = 43) or no glaucoma (n = 50) at an academic institution. The main outcome measure was the difference between the expected and the actual postoperative refraction.Results: Mean intraocular pressure (IOP) increased in trabeculectomy eyes from 8.7 ± 4.2 mm Hg to 10.7 ± 4.0 mm Hg (P < .0001), whereas it decreased in glaucoma control and normal control groups by 2.0 mm Hg (P = .003) and 2.1 mm Hg (P < .00001), respectively, with concurrent decrease in drops in the glaucoma control group (0.76 to 0.23, P < .0001). The difference from expected refractive outcome was −0.36 (more myopic) in trabeculectomy eyes compared with +0.23 (more hyperopic) in nonglaucoma controls and +0.40 in glaucoma controls (P < .0001). The correlation between change in IOP vs extent of refractive surprise was statistically significant (P = .01, r = −0.20). Final visual acuity was not affected by the difference in refractive error.Conclusions: The refractive surprise correlated to IOP change, with 2 mm Hg rise resulting in a −0.36 diopter shift between predicted and actual refraction. After cataract extraction, IOP decreased in controls and fewer drops were required, but IOP increased in the study group. Factors affecting refractive surprise in cataract surgery after trabeculectomy, especially IOP change and axial length, require further investigation.

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Color-Code Agreement Among Stratus, Cirrus, and Spectralis Optical Coherence Tomography in Relapsing-Remitting Multiple Sclerosis With and Without Prior Optic Neuritis – Corrected Proof

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Purpose: To evaluate the agreement of retinal nerve fiber layer (RNFL) color codes among Stratus, Cirrus, and Spectralis optical coherence tomography (OCT) in patients with relapsing-remitting multiple sclerosis.Design: Prospective cohort study.Methods: In 140 eyes from 70 patients having relapsing-remitting multiple sclerosis from January 2011 to September 2011, peripapillary RNFL thickness was measured using the fast RNFL program by Stratus, the optic disc cube protocol by Cirrus, and the N-site axonal analysis by Spectralis.Results: Overall, a moderate to good RNFL color code agreement was found (0.435-0.884), except for the nasal quadrant. The temporal quadrant was the most abnormal color coding by both Cirrus (64.7%) and Spectralis (61.7%) in both the optic neuritis (ON) and non-ON group and by Stratus (58.8%) in the ON group. Abnormal temporal RNFL color-code rate was significantly higher in ON eyes than non-ON eyes by Cirrus (P < .001), Stratus (P < .001), and Spectralis (P = .030). Overall, Cirrus significantly displayed abnormal findings while both Stratus and Spectralis displayed normal results for the inferior quadrant (P < .05). On the other hand, Spectralis OCT showed a significantly higher rate of abnormal findings while Cirrus displayed normal results for the temporal quadrant in non-ON eyes (P < .001).Conclusions: We found a substantial color-code disagreement among devices in patients with relapsing-remitting multiple sclerosis regarding the ON antecedent. In non-ON eyes, Spectralis yielded a significantly higher thinning for temporal quadrant than Cirrus, suggesting that N-site axonal analysis could define axonal damage in relapsing-remitting multiple sclerosis patients earlier than conventional RNFL analysis.

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