PURPOSE: Intravitreal bevacizumab is increasingly used to treat severe retinopathy of prematurity (ROP), but it enters the bloodstream, and there is concern that it may alter development of other organs. Previously we reported short-term outcomes of 61 infants enrolled in a dose de-escalation study, and we report the late recurrences and additional treatments. DESIGN: Masked, multicenter, dose de-escalation study. PARTICIPANTS: A total of 61 premature infants with type 1 ROP. METHODS: If type 1 ROP was bilateral at enrollment, then the study eye was randomly selected. In the study eye, bevacizumab intravitreal injections were given at de-escalating doses of 0.25 mg, 0.125 mg, 0.063 mg, or 0.031 mg; if needed, fellow eyes received 1 dose level higher: 0.625 mg, 0.25 mg, 0.125 mg, or 0.063 mg, respectively. After 4 weeks, additional treatment was at the discretion of the investigator. MAIN OUTCOME MEASURES: Early and late ROP recurrences, additional treatments, and structural outcomes after 6 months. RESULTS: Of 61 study eyes, 25 (41%; 95% confidence interval [CI], 29%-54%) received additional treatment: 3 (5%; 95% CI, 1%-14%) for early failure (within 4 weeks), 11 (18%; 95% CI, 9%-30%) for late recurrence of ROP (after 4 weeks), and 11 (18%; 95% CI, 9%-30%) for persistent avascular retina. Re-treatment for early failure or late recurrence occurred in 2 of 11 eyes (18%; 95% CI, 2%-52%) treated with 0.25 mg, 4 of 16 eyes (25%; 95% CI, 7%-52%) treated with 0.125 mg, 8 of 24 eyes (33%; 95% CI, 16%-55%) treated with 0.063 mg, and 0 (0%; 95% CI, 0%-31%) of 10 eyes treated with 0.031 mg. By 6 months corrected age, 56 of 61 study eyes had regression of ROP with normal posterior poles, 1 study eye had developed a Stage 5 retinal detachment, and 4 infants had died of preexisting medical conditions. CONCLUSIONS: Retinal structural outcomes are very good after low-dose bevacizumab treatment for ROP, although many eyes received additional treatment.

OBJECTIVE: To investigate the visual and anatomical outcomes of Boston keratoprosthesis (Kpro) type 1 reimplantation. DESIGN: Subgroup analysis of multicentre prospective cohort study. PARTICIPANTS: Of 303 eyes that underwent Kpro implantation between January 2003 and July 2008 by 1 of 19 surgeons at 18 medical centres, 13 eyes of 13 patients who underwent reimplantation of Boston Kpro type 1 were compared with 13 eyes of 13 diagnosis-matched patients who underwent initial implantation. METHODS: Forms reporting preoperative, intraoperative, and postoperative parameters were prospectively collected and analyzed. Main outcome measures were Kpro retention and logMAR visual acuity. RESULTS: After a mean follow-up time of 17.1 ± 17.6 months, the retention of both initial and repeat Kpro implantation was 92.3% (12/13 in both groups), and 62% of initial implantation and 58% of repeat implantation eyes achieved visual acuity better than 20/200. Vision worse than 20/200 was often due to glaucoma or posterior segment pathology. Best-recorded logMAR visual acuity was significantly improved postoperatively in both groups (p < 0.001), and there was no statistically significant difference in final logMAR visual acuity between the 2 groups (p = 0.89). Sterile keratolysis (n = 4) and fungal infection (n = 5) were the most common causes of initial Kpro failure in the repeat Kpro group. The single failure in the repeat Kpro implantation group was due to fungal keratitis, and in the control group it was related to Kpro extrusion. CONCLUSIONS: Repeat Kpro implantation is a viable option after failed initial Kpro, with visual and anatomical outcomes comparable to those of initial procedures.

PURPOSE OF REVIEW: Anterior visual pathway compression is a common feature of sellar region masses. We review the visual pathway neuroanatomy pertaining to sellar and parasellar lesions and describe recent advances in optical coherence tomography (OCT) imaging that have provided a novel quantitative perspective in the evaluation and management of such patients. RECENT FINDINGS: Ultrastructural measurements of optic nerve integrity using OCT, namely peripapillary retinal nerve fiber layer (pRNFL) and the ganglion cell and inner plexiform layer (GCIPL) thicknesses, have been shown to correlate with visual acuity and visual field deficits on perimetry in patients with compressive sellar region masses. In some cases, OCT can visualize early signs of anterior visual pathway involvement in the absence of clinically evident visual field loss or optic disc pallor. OCT is particularly useful when assessing patients who demonstrate less reliable visual field testing. Furthermore, there is growing awareness that pRNFL and GCIPL thinning preoperatively correlate with worse visual recovery following chiasmal decompression, highlighting the prognostic utility of OCT in this patient population. SUMMARY: OCT provides a complimentary, yet critical, role in quantitatively assessing ultrastructural retinal injury in patients with sellar and parasellar lesions compressing the anterior visual pathway and should be incorporated into routine evaluation.

PURPOSE: To evaluate long-term ocular surface clinical signs and symptoms response to therapy in patients with chronic ocular GVHD. METHODS: Retrospective review and data modeling. We reviewed the records of post-bone marrow transplantation patients who were newly diagnosed with ocular GVHD and initiated therapy, and analyzed changes in symptoms (Ocular Surface Disease Index [OSDI]; Symptom Assessment in Dry Eye [SANDE]) and signs (corneal fluorescein staining [CFS]; Schirmer test). We used a LOESS technique to fit a model in function of data variations and obtain a predictive value of the scores progression over time. RESULTS: The records of 123 patients who were followed-up for over 2 years (up to 62 months) were reviewed. The median baseline scores recorded were: OSDI 52 units, SANDE 62.2 units, CFS 2.0 Oxford units, and Schirmer 4 mm. After six months of follow up, scores improved for OSDI (-18.6 units, p = 0.007), SANDE (23.7 units, p = 0.01), and CFS (-0.7 Oxford units, p < 0.001). Data analysis showed that after a 2-year follow up the three parameters continued to improve: OSDI -13.67 units (27% reduction), SANDE -17.55 units (28%), CFS -1.1 units (54%), but Schirmer test scores progressively worsened -1.2 mm (22%). CONCLUSION: In patients with ocular GVHD symptoms and corneal fluorescein staining improved after initiation of treatment, meanwhile Schirmer scores declined progressively. This indicates that appropriate treatment in chronic ocular GVHD can lead to mid- and long-term improvements in symptoms and corneal epitheliopathy; however, sustained reduction in Schirmer test scores suggests chronic tear production impairment.

PURPOSE: Lipopolysaccharide (LPS), a bacterial endotoxin, is known to stimulate leuokotriene B4 (LTB4) secretion by human corneal (HCECs), conjunctival (HConjECs) and meibomian gland (HMGECs) epithelial cells. We hypothesize that this LTB4 effect represents an overall induction of proinflammatory gene expression in these cells. Our objective was to test this hypothesis. METHODS: Immortalized HCECs, HConjECs and HMGECs were cultured in the presence or absence of LPS (15 μg/ml) and ligand binding protein (LBP; 150 ng/ml). Cells were then processed for RNA isolation and the analysis of gene expression by using Illumina BeadChips, background subtraction, cubic spline normalization and GeneSifter software. RESULTS: Our findings show that LPS induces a striking increase in proinflammatory gene expression in HCECs and HConjECs. These cellular reactions are associated with a significant up-regulation of genes associated with inflammatory and immune responses (e.g. IL-1β, IL-8, and tumor necrosis factor), including those related to chemokine and Toll-like receptor signaling pathways, cytokine-cytokine receptor interactions, and chemotaxis. In contrast, with the exception of Toll-like signaling and associated innate immunity pathways, almost no proinflammatory ontologies were upregulated by LPS in HMGECs. CONCLUSIONS: Our results support our hypothesis that LPS stimulates proinflammatory gene expression in HCECs and HConjECs. However, our findings also show that LPS does not elicit such proinflammatory responses in HMGECs.

A 51-year-old man who had undergone right orbital decompression 5 months earlier developed a meningoencephalocele extending in the right sphenoid sinus through a skull base defect of the right ethmoid, sphenoid, and frontal bones. The authors report the third case to their knowledge of meningoencephalocele with cerebrospinal fluid leak after orbital decompression and discuss its management and measures that can be taken to prevent this rare but serious complication.

SIGNIFICANCE: Our survey found that participants with hemianopia report more difficulties watching video in various formats, including television (TV), on computers, and in a movie theater, compared with participants with normal vision (NV). These reported difficulties were not as marked as those reported by people with central vision loss. PURPOSE: The aim of this study was to survey the viewing experience (e.g., frequency, difficulty) of viewing video on TV, computers and portable visual display devices, and at the cinema of people with hemianopia and NV. This information may guide vision rehabilitation. METHODS: We administered a cross-sectional survey to investigate the viewing habits of people with hemianopia (n = 91) or NV (n = 192). The survey, consisting of 22 items, was administered either in person or in a telephone interview. Descriptive statistics are reported. RESULTS: There were five major differences between the hemianopia and NV groups. Many participants with hemianopia reported (1) at least "some" difficulty watching TV (39/82); (2) at least "some" difficulty watching video on a computer (16/62); (3) never attending the cinema (30/87); (4) at least some difficulty watching movies in the cinema (20/56), among those who did attend the cinema; and (5) never taking photographs (24/80). Some people with hemianopia reported methods that they used to help them watch video, including video playback and head turn. CONCLUSIONS: Although people with hemianopia report more difficulty with viewing video on TV and at the cinema, we are not aware of any rehabilitation methods specifically designed to assist people with hemianopia to watch video. The results of this survey may guide future vision rehabilitation.

MYF5 is member of the Myc-like basic helix-loop-helix transcription factor family and, in cooperation with other myogenic regulatory factors MYOD and MYF5, is a key regulator of early stages of myogenesis. Here, we report three consanguineous families with biallelic homozygous loss-of-function mutations in MYF5 who define a clinical disorder characterized by congenital ophthalmoplegia with scoliosis and vertebral and rib anomalies. The clinical phenotype overlaps strikingly with that reported in several Myf5 knockout mouse models. Affected members of two families share a haploidentical region that contains a homozygous 10 bp frameshift mutation in exon 1 of MYF5 (c.23_32delAGTTCTCACC [p.Gln8Leufs86]) predicted to undergo nonsense-mediated decay. Affected members of the third family harbor a homozygous missense change in exon 1 of MYF5 (c.283C>T [p.Arg95Cys]). Using in vitro assays, we show that this missense mutation acts as a loss-of-function allele by impairing MYF5 DNA binding and nuclear localization. We performed whole-genome sequencing in one affected individual with the frameshift mutation and did not identify additional rare variants in the haploidentical region that might account for differences in severity among the families. These data support the direct role of MYF5 in rib, spine, and extraocular muscle formation in humans.

Purpose: To evaluate the deeper choroidal vasculature in eyes with various ocular disorders using spectral domain (SD) optical coherence tomography angiography (OCTA) and swept source (SS) OCTA. Methods: Patients underwent OCTA imaging with either SD-OCTA (Zeiss Cirrus Angioplex or Optovue AngioVue) or SS-OCTA (Topcon Triton). Retinal pigment epithelium (RPE) integrity, structural visualization of deep choroidal vessels on en face imaging, and OCTA of deep choroidal blood flow signal were analyzed. Choroidal blood flow was deemed present if deeper choroidal vessels appeared bright after appropriate segmentation. Results: Structural visualization of choroidal vessels was feasible in all eyes by en face imaging. In both SD-OCTA and SS-OCTA, choroidal blood flow signal was present in all eyes with overlying RPE atrophy (100% of eyes with RPE atrophy, 28.6% of all imaged eyes, P < .001). Conclusions: While choroidal vessels can be visualized anatomically in all eyes by en face imaging, choroidal blood flow detection in deep choroidal vessel is largely restricted to areas with overlying RPE atrophy. Intact RPE acts as a barrier for reliable detection of choroidal flow using current OCTA technology, inhibiting evaluation of flow in deeper choroidal vessels in most eyes.

Purpose: To identify genetic risk factors contributing to central corneal thickness (CCT) in individuals from South India, a population with a high prevalence of ocular disorders. Methods: One hundred ninety-five individuals from 15 large South Indian pedigrees were genotyped using the Omni2.5 bead array. Family-based association for CCT was conducted using the score test in MERLIN. Results: Genome-wide association study (GWAS) identified strongest association for single nucleotide polymorphisms (SNPs) in the first intron of WNT7B and CCT (top SNP rs9330813; β = -0.57, 95% confidence interval [CI]: -0.78 to -0.36; P = 1.7 × 10-7). We further investigated rs9330813 in a Latino cohort and four independent European cohorts. A meta-analysis of these data sets demonstrated statistically significant association between rs9330813 and CCT (β = -3.94, 95% CI: -5.23 to -2.66; P = 1.7 × 10-9). WNT7B SNPs located in the same genomic region that includes rs9330813 have previously been associated with CCT in Latinos but with other ocular quantitative traits related to myopia (corneal curvature and axial length) in a Japanese population (rs10453441 and rs200329677). To evaluate the specificity of the observed WNT7B association with CCT in the South Indian families, we completed an ocular phenome-wide association study (PheWAS) for the top WNT7B SNPs using 45 ocular traits measured in these same families including corneal curvature and axial length. The ocular PheWAS results indicate that in the South Indian families WNT7B SNPs are primarily associated with CCT. Conclusions: The results indicate robust evidence for association between WNT7B SNPs and CCT in South Indian pedigrees, and suggest that WNT7B SNPs can have population-specific effects on ocular quantitative traits.