Category: Peer-reviewed

Meibomian Gland Morphology in Japanese Infants, Children, and Adults Observed Using a Mobile Pen-shaped Infrared Meibography Device – Corrected Proof

Purpose: To compare meibomian gland morphology between children and adults.Design: Cross-sectional, observational case series.Methods: In an institutional setting, healthy pediatric (n = 78, 30 boys, 48 girls; mean age ± standard deviation, 4.1 ± 3.4 years; range 1 month – 12 years) and adult (n = 25, 11 men, 14 women; 31.3 ± 4.8 years; range 24-39 years) volunteers participated in the study. A noninvasive mobile pen-shaped infrared meibography device was used to observe the meibomian glands. Lost meibomian gland area (meiboscore) was scored from grade 0 (no meibomian gland loss) through grade 3 (>two-thirds of the total area lost). The number of meibomian glands in each eyelid was counted by reviewing the video. Eyelid width was measured using a ruler. Meibomian gland density was calculated as the number of meibomian glands divided by the eyelid width.Results: The numbers of meibomian glands in the upper/lower eyelids were 26.9 ± 3.9 / 22.0 ± 2.2 in the pediatric group and 28.1 ± 2.7 / 24.4 ± 2.6 in the adult group (P = .22, P < .0001). Eyelid width was 24.4 ± 2.4 mm in the pediatric group and 27.9 ± 1.57 mm in the adult group (P < .0001). Meibomian gland densities in the upper/lower eyelids were 1.09 ± 0.17 / 0.91 ± 0.11 in the pediatric group and 1.01 ± 0.12 / 0.88 ± 0.10 in the adult group (P = .03, P = .45).Conclusions: The mobile pen-shaped infrared meibography device is useful for obtaining information on the meibomian gland structure, not only in adults but also in children, including infants. The morphology of the meibomian glands in children was the same as that in adults, distributing across the whole tarsal plates in both the upper and lower eyelids.

16 and 24 Gy Low-voltage X-ray Irradiation With Ranibizumab Therapy for Neovascular Age-Related Macular Degeneration: 12-Month Outcomes – Corrected Proof

Purpose: To describe the 12-month safety and efficacy outcomes of 16 or 24 Gy radiation using low-voltage x-ray irradiation in conjunction with intravitreal ranibizumab for neovascular age-related macular degeneration (AMD).Design: Prospective, phase I, open-label, nonrandomized uncontrolled safety study.Methods: setting: Institutional. study population: Neovascular AMD patients. intervention: One x-ray irradiation treatment at 16 or 24 Gy was administered externally through 3 locations in the inferior pars plana. After 2 initial monthly loading doses of ranibizumab, subsequent ranibizumab was administered according to predetermined criteria. main outcome measures: Visual acuity, number of ranibizumab injections, safety and efficacy metrics at 12 months.Results: Forty-seven eyes of 47 patients were enrolled and completed 12 months of follow-up: 16 Gy (n = 28) and 24 Gy (n = 19). There was no evidence of radiation retinopathy, optic neuropathy, or cataract. The mean visual acuity improved in both groups: +8.4 ± 11.9 letters and +7.8 ± 12 letters for 16 and 24 Gy, respectively. In both groups, 100% of subjects lost <15 letters, with 76% and 79% gaining ≥0 letters in the 16 Gy and 24 Gy groups, respectively. Patients received a mean of 1.0 additional injection over 12 months. The mean change in optical coherence tomography central subfield thickness from baseline to month 12 was −107 and −87 μm for the 16 Gy and 24 Gy groups, respectively.Conclusion: One treatment of 16 or 24 Gy low-voltage x-ray therapy with as-needed ranibizumab appears safe in subjects with neovascular AMD at 12 months. An overall improvement in visual acuity was observed. No radiation-related adverse effects were reported.

Three-Year Follow-up after Unilateral Subretinal Delivery of Adeno-Associated Virus in Patients with Leber Congenital Amaurosis Type 2 – Corrected Proof

Objective:
The aim of this study was to show the clinical data of long-term (3-year) follow-up of 5 patients affected by Leber congenital amaurosis type 2 (LCA2) treated with a single unilateral injection of adeno-associated virus AAV2-hRPE65v2.

Design:
Clinical trial.

Participants:
Five LCA2 patients with RPE65 gene mutations.

Methods:
After informed consent and confirmation of trial eligibility criteria, the eye with worse visual function was selected for subretinal delivery of adeno-associated virus (AAV2-hRPE65v2). Subjects were evaluated before and after surgery at designated follow-up visits (1, 2, 3, 14, 30, 60, 90, 180, 270, and 365 days, 1.5 years, and 3 years) by complete ophthalmic examination. Efficacy for each subject was monitored with best-corrected visual acuity, kinetic visual field, nystagmus testing, and pupillary light reflex.

Main Outcome Measures:
Best-corrected visual acuity, kinetic visual field, nystagmus testing, and pupillary light reflex.

Results:
The data showed a statistically significant improvement of best-corrected visual acuity between baseline and 3 years after treatment in the treated eye (P<0.001). In all patients, an enlargement of the area of visual field was observed that remained stable until 3 years after injection (average values: baseline, 1058 deg2 vs. 3 years after treatment, 4630 deg2) and a reduction of the nystagmus frequency compared with baseline at the 3-year time point. Furthermore, a statistically significant difference was observed in the pupillary constriction of the treated eye (P<0.05) compared with the untreated eye in 3 patients at 1- and 3-year time points. No patients experienced serious adverse events related to the vector in the 3-year postinjection period.

Conclusions:
The long-term follow-up data (3 years) on the 5-patient Italian cohort involved in the LCA2 gene therapy clinical trial clearly showed a stability of improvement in visual and retinal function that had been achieved a few months after treatment. Longitudinal data analysis showed that the maximum improvement was achieved within 6 months after treatment, and the visual improvement was stable up to the last observed time point.

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

Detection of Glaucomatous Progression by Spectral-Domain Optical Coherence Tomography – Corrected Proof

Purpose:
To compare the rate of change of circumpapillary retinal nerve fiber layer (cRNFL) thickness, macular volume and thickness, and optic nerve head (ONH) parameters assessed using spectral-domain optical coherence tomography (SD-OCT) between eyes with progressing and nonprogressing glaucoma.

Design:
Longitudinal, observational study.

Participants:
Two hundred seventy-nine eyes from 162 glaucoma patients followed for an average of 2.2 years.

Methods:
Eyes were classified as progressors and nonprogressors according to assessment of optic disc and RNFL photographs and visual field progression analysis. Linear mixed effects models were used to evaluate the overall rate of change of cRNFL thickness, macular volume and thickness, and ONH parameters after adjustment for age, spherical equivalent, signal strength, and baseline SD-OCT measurements.

Main Outcome Measures:
The rate of change of cRNFL thickness, macular volume, and thickness and ONH parameters.

Results:
Sixty-three eyes (22.6%) from 52 subjects were identified as progressors. Average, inferior quadrant, and 6- and 7-o’clock sector cRNFL thickness decreased faster in progressors than in nonprogressors (−1.26 vs −0.94, −2.47 vs −1.75, −3.60 vs −2.52, and −2.77 vs −1.51 μm/year, respectively; all P<0.05). The ONH rim area decreased faster, and average and vertical cup-to-disc ratio increased faster in progressors than in nonprogressors (−0.016 vs −0.006 mm2/year, and 0.004 vs 0.002 and 0.006 vs 0.004 per year, respectively; all P<0.05). Macular cube volume and the thickness of temporal outer and inferior inner macular sectors decreased faster in progressors than in nonprogressors (−0.068 vs −0.048 mm3/year, and −2.27 vs −1.67 and −2.51 vs −1.73 μm/year, respectively; all P<0.05).

Conclusions:
Serial measurement of parameters in all 3 areas (cRNFL, macula, and ONH) by SD-OCT may permit identification of progression in glaucomatous eyes.

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

The Singapore 5-Fluorouracil Trial: Intraocular Pressure Outcomes at 8 Years – Corrected Proof

Objective:
To report the 8-year outcomes of Asian subjects who underwent trabeculectomy augmented by intraoperative 5-fluorouracil (5-FU) or placebo.

Design:
Retrospective review of a randomized controlled trial.

Participants:
Subjects with primary open-angle or angle-closure glaucoma.

Methods:
Study subjects were prospectively followed up for 3 years. After the last subject recruited had completed 8 years of follow-up, the charts of all subjects were reviewed to capture data from the year 3 visit onward. Kaplan–Meier survival function with Cox regression was performed to identify risk factors associated with trabeculectomy failure at 8 years.

Main Outcome Measures:
The primary outcome was trabeculectomy failure defined as intraocular pressure (IOP) >21 or <6 mmHg on 2 consecutive occasions after the first 6 weeks after surgery, repeat glaucoma surgery, or loss of light perception. Further end points were defined at IOP levels >17 and >14 mmHg. Secondary outcomes included IOP at 8 years and number of glaucoma medications. Complete success was defined using IOP end points ≤21, ≤17, or ≤14 mmHg at 8 years without medications.

Results:
Of the 243 enrolled subjects, 170 (70.0%) completed 8 years follow-up, 86 in the 5-FU and 84 in the placebo group. There was no significant difference in failure rates at 8 years for the failure definitions of IOP >21 mmHg (11.6% of the 5-FU group vs. 16.7% of the placebo group; P = 1.00), IOP >17 mmHg (23.3% of the 5-FU group vs. 31% of the placebo group; P = 0.78), and IOP >14 mmHg (46.5% of the 5-FU group vs. 58.3% of the placebo group; P = 0.37). Mean IOP at 8 years was 13.7 mmHg in the 5-FU versus 14.4 mmHg in the placebo group (P = 0.24). Mean number of medications was 0.65 drops in the 5-FU versus 0.93 drops in the placebo group (P = 0.06). Complete success with IOP ≤21 mmHg at 8 years was achieved in 48 subjects (55.8%) in the 5-FU and 33 subjects (39.3%) in the placebo group (P = 0.09). Absence of bleb microcysts at 1 year, preoperative IOP, and number of bleb needlings performed within the first year were significantly associated with failure.

Conclusions:
There was no significant difference in IOP between the 5-FU and the placebo group at 8 years.

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

Ultrathin Descemet’s Stripping Automated Endothelial Keratoplasty with the Microkeratome Double-Pass Technique: Two-Year Outcomes – Corrected Proof

Purpose:
To evaluate the outcomes and graft survival rates after ultrathin (UT) Descemet’s stripping automated endothelial keratoplasty (DSAEK) using the microkeratome-assisted double-pass technique.

Design:
Prospective, consecutive, interventional case series.

Participants:
Patients with endothelial decompensation of various causes (Fuchs endothelial dystrophy, pseudophakic or aphakic bullous keratopathy, failed previous graft, herpetic endotheliitis, or buphthalmus; n = 285 grafts).

Intervention:
Donor preparation was performed using the microkeratome-assisted double-pass technique. Stripping of the Descemet’s membrane was performed under air and the graft was delivered into the anterior chamber using the pull-through technique through a 3-mm clear-cornea incision using a modified Busin glide.

Main Outcome Measures:
Best spectacle-corrected visual acuity (BSCVA), manifest refraction, endothelial cell density, and graft thickness (GT).

Results:
Excluding all eyes with pre-existing ocular comorbidities, mean BSCVA at 3, 6, 12, and 24 months was 0.16, 0.11, 0.08, and 0.04 logarithm of the minimum angle of resolution units, respectively. The percentage of patients achieving BSCVA of 20/20 or better at 3, 6, 12, and 24 months was 12.3%, 26.3%, 39.5%, and 48.8%, respectively. A statistically significant (P < 0.0001) hyperopic shift of 0.78 ± 0.59 diopters (D; range, −0.75 to 1.75 D) was found at 1 year. The endothelial cell loss at 3, 6, 12, and 24 months was 29.8 ± 14.3%, 33 ± 15.5%, 35.6 ± 14.1%, and 36.6 ± 16.0%, respectively. The mean central GT recorded 3 months after surgery was 78.28 ± 28.89 μm. Complications included microkeratome failure to achieve perfect dissection in 21 donor tissues (7.2%), with 6 (2.1%) being discarded; total graft detachment in 11 cases (3.9%); primary failure in 4 cases (1.4%); and secondary failure in 4 additional cases (1.4%). Kaplan-Meier cumulative probability of a rejection episode at 3, 6, 12, and 24 months was 0%, 0.4%, 2.4%, and 3.3%, respectively.

Conclusions:
The visual outcomes of UT DSAEK are comparable with those published for Descemet’s membrane endothelial keratoplasty and better than those reported after DSAEK in terms of both speed of visual recovery and percentage of patients with 20/20 final visual acuity. However, unlike with Descemet’s membrane endothelial keratoplasty, preparation and delivery of donor tissue are neither difficult nor time consuming. Complications of UT DSAEK do not differ substantially from those recorded with standard DSAEK but are much less frequent than those reported after Descemet’s membrane endothelial keratoplasty.

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

Author reply

We thank Hong et al for their interest in our paper “Shifting Trends in Bacterial Keratitis in Toronto, an 11 Year Review.” In our paper, we reviewed the microbiology records of 1701 consecutive corneal scrapings; our main findings were a significa…

Author reply

We thank Hong et al for their comments regarding our manuscript and would like to address several important issues that they raise. The focus of our paper was specifically to study keratoplasty among patients with corneal endothelial disease (CED). Exp…