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: To evaluate the changes in anterior corneal topography induced by short-time wear of scleral contact lenses (SLs) in keratoconic subjects with and without a history of corneal cross-linking (CXL). METHODS: Nine keratoconic patients (14 eyes) were fitted with 18.5 mm SLs for optical rehabilitation. Subjects were divided into 2 groups: 7 eyes without a history of CXL (Non-CXL group) and 7 with a history of CXL (CXL group). Corneal topography was performed at baseline and after 2 and 5 hours of lens wear. The differences for simulated flat (Kflat), steep (Ksteep) and maximal (Kmax) corneal curvatures, central corneal astigmatism (CCA), and central cornea thickness were evaluated. RESULTS: No statistically significant difference was detected between Non-CXL and CXL groups in any of these measures. Statistically significant flattening was detected in Ksteep Repeated measures analysis of variance ([RM-ANOVA), F (2,24) = 11.32, P < 0.0001], CCA [RM-ANOVA, F (2,24) = 15.34, P < 0.0001], and Kmax [RM-ANOVA, F (2,24) = 19.10, P < 0.0001). From baseline to 5 hours of SL wear, Ksteep decreased on average from 53.1 to 52.4 D, Kmax decreased from 56.7 to 55.8 D, and CCA decreased from 7.2 to 6.3 D. Kmax showed a trend toward more flattening in the Non-CXL group. Central cornea thickness showed significant thickening over time from baseline (451 μm) to 5 hours (458 μm) of SL wear [RM-ANOVA, F (1,12) = 319.3, P < 0.0001]. CONCLUSIONS: Short-term scleral lens wear in keratoconic patients may cause flattening of the anterior cornea. A history of CXL treatment does not guarantee corneal shape stability after scleral lens wear. Practitioners should be aware of these changes because scleral lens wear may mask the signs of keratoconus progression.

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.

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.

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 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.

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.

Considerable improvement has been achieved in the way in which exudative age-related macular degeneration is conventionally treated and in the associated visual outcomes and prognosis, thanks to the agents with effects against vascular endothelial growth factor (anti-VEGF). By comparison to earlier treatment approaches that involved the use of lasers, the anti-VEGF agents have made it possible to accomplish more positive visual and anatomical outcomes in cases of exudative age-related macular degeneration. Indeed, owing to their positive effects, anti-VEGF agents have quickly come to be considered the gold standard for the treatment of wet age-related macular degeneration. Aflibercept, the most recently approved intravitreally administered anti-VEGF, seems to mark another milestone in the treatment of wet age-related macular degeneration. This anti-VEGF agent presents a series of singular pharmacodynamic and pharmacokinetic attributes that provide it a number of biological benefits in relation to the treatment of choroidal neovascularization compared to other agents. These attributes include high level of affinity for the VEGF-A factor, an intravitreal half-life of great length, as well as the ability to serve as an antagonist for other growth factors besides VEGF. The impact of Aflibercept on the manner in which exudative age-related macular degeneration is managed was demonstrated by thoroughly reviewing the related literature. The present review article highlights the pharmacology, pharmacokinetics, safety and effectiveness of this anti-VEGF agent as well as the landmark clinical studies that have been carried out to establish this drug as a gold standard in the therapy of neovascular age-related macular degeneration. In addition, studies regarding the outcomes and effectiveness of the various dosage regimens, either as monotherapy or in combination with other agents, are also reviewed.

BACKGROUND: Orbital cavernous hemangiomas (OCH) are the most common adult orbital tumor and represent an ideal index lesion for endonasal orbital tumor surgery. In order to standardize outcomes reporting, an anatomic-based staging system was developed. METHODS: An international, multidisciplinary panel of 23 experts in orbital tumor surgery was formed. A modified Delphi method was used to develop the cavernous hemangioma exclusively endonasal resection (CHEER) staging system with a total of 2 rounds being completed. RESULTS: Tumors medial to a plane along the long axis of the optic nerve may be considered amenable for an exclusively endonasal resection. In select cases, tumors may extend inferolaterally if the tumor remains below a plane from the contralateral naris through the long axis of the optic nerve (ie, plane of resectability [POR]). This definition reached consensus with 91.3% of panelists in agreement. Five stages were designed based on increasing technical resection difficulty and potential for morbidity. Stages were based on the relationship of the tumor to the extraocular muscles, the inferomedial muscular trunk of the ophthalmic artery (IMT), and orbital foramina. Staging by anatomic location also reached consensus with 87.0% of panelists in agreement. Size was not included in the staging system due to the lack of agreement on the contribution of size to resection difficulty. CONCLUSION: Endoscopic orbital tumor surgery is a nascent field with a growing, yet heterogeneous, body of literature. The CHEER staging system is designed to facilitate international, high-quality, standardized studies establishing the safety, efficacy, and outcomes of endonasal resection of OCH.