Blindness due to corneal diseases is a common pathology affecting up to 23 million individuals worldwide. The tissue-engineered anterior human cornea, which is currently being tested in a Phase I/II clinical trial to treat severe corneal trophic ulcers with preliminary good feasibility and safety results. This bioartificial cornea is based on a nanostructured fibrin-agarose biomaterial containing human allogeneic stromal keratocytes and cornea epithelial cells, mimicking the human native anterior cornea in terms of optical, mechanical, and biological behavior. This product is manufactured as a clinical-grade tissue engineering product, fulfilling European requirements and regulations. The clinical translation process included several phases: an initial in vitro and in vivo preclinical research plan, including preclinical advice from the Spanish Medicines Agency followed by additional preclinical development, the adaptation of the biofabrication protocols to a good manufacturing practice manufacturing process, including all quality controls required, and the design of an advanced therapy clinical trial. The experimental development and successful translation of advanced therapy medicinal products for clinical application has to overcome many obstacles, especially when undertaken by academia or SMEs. We expect that our experience and research strategy may help future researchers to efficiently transfer their preclinical results into the clinical settings.

PURPOSE: Epiretinal proliferation is a distinct clinical entity from epiretinal membrane that classically is associated with lamellar macular holes, but its prevalence and association with full-thickness macular holes (FTMH) have not been well described. We characterized macular hole-associated epiretinal proliferation (MHEP) and its effects on long-term surgical outcomes. DESIGN: Multicenter, interventional, retrospective case-control study. PARTICIPANTS: Consecutive eyes that underwent surgery for FTMH with a minimum of 12 months follow-up. METHODS: All eyes underwent pars plana vitrectomy, removal of any epiretinal membranes, and gas tamponade, with or without internal limiting membrane (ILM) peeling. Spectral-domain OCT imaging was obtained before and after surgery. MAIN OUTCOME MEASURES: Improvement in visual acuity and single-surgery hole closure rates in eyes with, versus without, MHEP at 12 months. RESULTS: Seven hundred twenty-five charts were analyzed, and 113 patients met inclusion criteria. Of 113 eyes with FTMH, 30 (26.5%) showed MHEP. Patients with FTMH and MHEP were older (P < 0.002) and more often men (P = 0.001), and showed more advanced macular hole stages than those without MHEP (P = 0.010). A full posterior vitreous detachment was more common in eyes with MHEP (P < 0.004). Twelve months after surgery, FTMH with MHEP patients showed significantly less improvement in visual acuity (P = 0.019) with higher rates of ellipsoid and external limiting membrane defects (P < 0.05) and with a higher rate of failure to close with 1 surgery compared to FTMH without MHEP (26.7% vs. 4.8%; P = 0.002]). Peeling the ILM was associated with improved rates of hole closure in FTMH with MHEP (P < 0.001). Multivariate testing confirmed that the presence of MHEP was an independent risk factor for less visual improvement (P = 0.031) and for single-surgery nonclosure (P = 0.009) and that ILM peeling improved single-surgery closure rates (P = 0.026). CONCLUSIONS: We found that FTMH with MHEP showed poorer anatomic and visual outcomes after vitrectomy compared with FTMH without MHEP. Internal limiting membrane peeling was associated with improved closure rates and should be considered when MHEP is detected before surgery.

BACKGROUND: Preterm infants with anaemia are treated with recombinant human erythropoietin (rhEPO). It is debated whether rhEPO treatment is a risk factor for retinopathy of prematurity (ROP). We evaluated longitudinal EPO and haemoglobin levels, blood transfusions and neonatal morbidities as risk factors for severe ROP. METHOD: This prospective study included 78 Swedish infants, born <28 weeks gestational age (GA), screened for ROP. We tested serum EPO levels on postnatal days 1, 7, 14 and 28 and at postmenstrual ages 32, 36 and 40 weeks. Haemoglobin levels and blood transfusions were recorded during postnatal weeks 1-4. Anaemia was defined as haemoglobin ≤110 g/L. RESULTS: During postnatal week 1, infants with severe ROP requiring treatment (28%) more frequently developed anaemia (42.9% versus 8.0%, P = 0.003) and had higher mean EPO levels (postnatal day 7: 14.2 versus 10.8 mIU/mL, P = 0.003) compared to infants with no or less severe ROP not requiring treatment. In multivariable analyses, GA and anaemia during week 1 remained significant risk factors, but elevated EPO level postnatal day 7 was no longer significant. CONCLUSIONS: Among infants born <28 weeks GA, anaemia during week 1 was a significant risk factor for severe ROP requiring treatment but not elevated EPO levels.

Tree shrews are small mammals with excellent vision and are closely related to primates. They have been used extensively as a model for studying refractive development, myopia, and central visual processing and are becoming an important model for vision research. Their cone dominant retina (∼95% cones) provides a potential avenue to create new damage/disease models of human macular pathology and to monitor progression or treatment response. To continue the development of the tree shrew as an animal model, we provide here the first measurements of higher order aberrations along with adaptive optics scanning light ophthalmoscopy (AOSLO) images of the photoreceptor mosaic in the tree shrew retina. To compare intra-animal in vivo and ex vivo cone density measurements, the AOSLO images were matched to whole-mount immunofluorescence microscopy. Analysis of the tree shrew wavefront indicated that the optics are well-matched to the sampling of the cone mosaic and is consistent with the suggestion that juvenile tree shrews are nearly emmetropic (slightly hyperopic). Compared with in vivo measurements, consistently higher cone density was measured ex vivo, likely due to tissue shrinkage during histological processing. Tree shrews also possess massive mitochondria ("megamitochondria") in their cone inner segments, providing a natural model to assess how mitochondrial size affects in vivo retinal imagery. Intra-animal in vivo and ex vivo axial distance measurements were made in the outer retina with optical coherence tomography (OCT) and transmission electron microscopy (TEM), respectively, to determine the origin of sub-cellular cone reflectivity seen on OCT. These results demonstrate that these megamitochondria create an additional hyper-reflective outer retinal reflective band in OCT images. The ability to use noninvasive retinal imaging in tree shrews supports development of this species as a model of cone disorders.

PURPOSE: To assess the potential of ready-made (spherical) spectacles (RMS) in meeting the need for refractive correction in visually impaired children in China. METHODS: Eligible children aged 5-17 years were identified from the three study sites in China. Distance visual acuity was measured with a retroilluminated logarithm of the minimum angle of resolution chart with tumbling E optotypes. Cycloplegic autorefraction was performed on all children using a handheld autorefractor. If uncorrected visual acuity (UCVA) was ≤20/40 in either eye, best corrected visual acuity was measured with subjective refractive error. RESULTS : A total of 13 702 children were enumerated from the three studies, with 12 334 (90.0%) having both reliable visual acuity measurements and successful cycloplegia. Among the 12 334 study children, the prevalence of UCVA ≤20/40 in the better seeing eye was 16.4% (95% CI 15.0% to 17.8%), with 91.1% (1843) of these improving by ≥3 lines of visual acuity with refractive correction. Prevalence was 12.7% (95% CI 11.5% to 13.9%) for UCVA 20/50 with 97.4% (1521) improving by ≥3 lines, and 9.38% (95% CI 8.39% to 19.4%) for UCVA ≤20/63 with 98.4% (1138) improving by ≥3 lines. Depending on the severity of visual impairment, 62.8%-64.0% of children could be accommodated with RMS if not correcting for astigmatism of ≤0.75 dioptres and anisometropia of ≤0.50 spherical equivalent dioptres. Approximately 87% of children could be accommodated with RMS if astigmatism and anisometropia limits were increased to ≤1.25 and ≤1.50 dioptres, respectively. CONCLUSIONS: RMS could substantially alleviate visual morbidity in two-thirds or more of visually impaired schoolchildren in China. This cost-effective approach to refractive correction might also be useful in low/middle-income countries with poor access to optometric services.

PURPOSE OF REVIEW: Impaired eye movements are frequently seen in ophthalmic and neurologic clinical practice, especially in individuals with movement disorders. Identification of the abnormal movement can aid initial diagnosis and improve understanding of the underlying disease pathophysiology. The present article reviews the ocular motor manifestations and recent research on them in common movement disorders. RECENT FINDINGS: Ocular motor manifestations and their pathophysiologic correlates are being defined. In particular, study of eye movements can help clarify the changing clinicopathologic spectrum of atypical parkinsonian disorders. The pathophysiology and natural history of blepharospasm are being elucidated. Recent research focuses on high-resolution imaging and other technological advances to improve the sensitivity of the ocular motility exam. Eye movements are being studied as biomarkers for diagnosis and progression in clinical care and trials. SUMMARY: The current review summarizes ocular motor manifestations in common movement disorders, and presents recent research investigating their cause and treatment.

PURPOSE: To describe the clinical spectrum, clinicopathological correlation and outcomes of different surgical strategies in the management of acquired implantation iris cysts. METHODS: From 1 January 1989 to 31 December 2015, 27 patients (27 eyes) with acquired implantation iris cysts underwent surgery. The charts were reviewed for demographics, preoperative characteristics, surgical approach, histopathological records of excised cyst and postoperative outcomes. RESULTS: The median age at presentation was 5 years (IQR: 1.3-14 years). Out of 27 patients, 21 (78%) were aged≤18 years. Almost two-third (17/27, 63%) patients had history of penetrating ocular trauma prior to surgery. All patients underwent cyst aspiration combined with complete cyst excision with additional surgical procedures when necessary. Along with complete cyst excision, sector iridectomy was performed in 20/27 (74%) eyes. At a median postoperative follow-up period of 8 months (range: 1-72 months), recurrence was noted in 3/27 (11%) cases at a mean follow-up period of 2.3±1.5 months postsurgery. Eyes in which sector iridectomy was performed had lower incidence of recurrence, and this was statistically significant (p=0.03). However, the improvement in best-corrected visual acuity postoperatively was not statistically significant (p=0.15). CONCLUSION: Acquired implantation iris cysts are associated with significant ocular morbidity. Complete excision of the cyst with sector iridectomy is an effective treatment option if other less invasive surgical approaches fail. Visual acuity can be significantly improved but is typically limited due to associated comorbidities.

: Amblyopia and strabismus affect 2%-5% of the population and cause a broad range of visual deficits. The response to treatment is generally assessed using visual acuity, which is an insensitive measure of visual function and may, therefore, underestimate binocular vision gains in these patients. On the other hand, the contrast sensitivity function (CSF) generally takes longer to assess than visual acuity, but it is better correlated with improvement in a range of visual tasks and, notably, with improvements in binocular vision. The present study aims to assess monocular and binocular CSFs in amblyopia and strabismus patients. : Both monocular CSFs and the binocular CSF were assessed for subjects with amblyopia ( = 11), strabismus without amblyopia ( = 20), and normally sighted controls ( = 24) using a tablet-based implementation of the quick CSF, which can assess a full CSF in <3 min. Binocular summation was evaluated against a baseline model of simple probability summation. : The CSF of amblyopic eyes was impaired at mid-to-high spatial frequencies compared to fellow eyes, strabismic eyes without amblyopia, and control eyes. Binocular contrast summation exceeded probability summation in controls, but not in subjects with amblyopia (with or without strabismus) or strabismus without amblyopia who were able to fuse at the test distance. Binocular summation was less than probability summation in strabismic subjects who were unable to fuse. : We conclude that monocular and binocular contrast sensitivity deficits define important characteristics of amblyopia and strabismus that are not captured by visual acuity alone and can be measured efficiently using the quick CSF.

Age-related macular degeneration (AMD) is the most common cause of blindness among the elderly in the developed world. While treatment is effective for the neovascular or "wet" form of AMD, no therapy is successful for the non-neovascular or "dry" form. Here we discuss the current knowledge on dry AMD pathobiology and propose future research directions that would expedite the development of new treatments. In our view, these should emphasize system biology approaches that integrate omic, pharmacological, and clinical data into mathematical models that can predict disease onset and progression, identify biomarkers, establish disease causing mechanisms, and monitor response to therapy.

PURPOSE: To compare mycophenolate mofetil (MMF) to methotrexate (MTX) as corticosteroid-sparing therapy for ocular inflammatory diseases. DESIGN: Retrospective analysis of cohort study data. METHODS: Participants were identified from the Systemic Immunosuppressive Therapy for Eye Diseases Cohort Study. Demographic and clinical characteristics were obtained via medical record review. The study included 352 patients who were taking single-agent immunosuppression with MTX or MMF at 4 tertiary uveitis clinics. Marginal structural models (MSM)-derived statistical weighting created a virtual population with covariates and censoring patterns balanced across alternative treatments. With this methodological approach, the results estimate what would have happened had none of the patients stopped their treatment. Survival analysis with stabilized MSM-derived weights simulated a clinical trial comparing MMF vs MTX for noninfectious inflammatory eye disorders. The primary outcome was complete control of inflammation on prednisone ≤10 mg/day, sustained for ≥30 days. RESULTS: The time to success was shorter (more favorable) for MMF than MTX (hazard ratio = 0.68, 95% confidence interval: 0.46-0.99). Adjusting for covariates, the proportion achieving success was higher at every point in time for MMF than MTX from 2 to 8 months, then converges at 9 months. The onset of corticosteroid-sparing success took more than 3 months for most patients in both groups. Outcomes of treatment (MMF vs MTX) were similar across all anatomic sites of inflammation. The incidence of stopping therapy for toxicity was similar in both groups. CONCLUSIONS: Our results suggest that, on average, MMF may be faster than MTX in achieving corticosteroid-sparing success in ocular inflammatory diseases.