Corneal neurotization is an innovative surgical approach for restoring corneal sensation, whereby the sensory functions of a normal donor nerve are rerouted to an anesthetic cornea. Many variations upon this basic surgical principal have been introduced and have proven successful in ameliorating corneal sensation in patients. It is unclear whether one surgical approach is superior to another, as each has advantages and disadvantages. Surgical approaches differ in the donor nerve selected and in whether a nerve graft is required. Surgical techniques have varied in the location, number and extent of incisions, methods of nerve coaptation, the number of surgeons required, the equipment and materials utilized and the duration of the procedure. The current review provides an overview of developments in this nascent field. A review of all peer-reviewed publications on corneal neurotization was performed. The various approaches to corneal neurotization are compared and discussed. The least morbid, simplest, most expedient and successful surgical approaches will ultimately become the most utilized.

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.

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.

Late-onset retinal degeneration (L-ORD) is an autosomal dominant macular degeneration characterized by the formation of sub-retinal pigment epithelium (RPE) deposits and neuroretinal atrophy. L-ORD results from mutations in the C1q-tumor necrosis factor-5 protein (CTRP5), encoded by the CTRP5/C1QTNF5 gene. To understand the mechanism underlying L-ORD pathology, we used a human cDNA library yeast two-hybrid screen to identify interacting partners of CTRP5. Additionally, we analyzed the Bruch's membrane/choroid (BM-Ch) from wild-type (Wt), heterozygous S163R Ctrp5 mutation knock-in (Ctrp5 ), and homozygous knock-in (Ctrp5 ) mice using mass spectrometry. Both approaches showed an association between CTRP5 and HTRA1 via its C-terminal PDZ-binding motif, stimulation of the HTRA1 protease activity by CTRP5, and CTRP5 serving as an HTRA1 substrate. The S163R-CTRP5 protein also binds to HTRA1 but is resistant to HTRA1-mediated cleavage. Immunohistochemistry and proteomic analysis showed significant accumulation of CTRP5 and HTRA1 in BM-Ch of Ctrp5 and Ctrp5 mice compared with Wt. Additional extracellular matrix (ECM) components that are HTRA1 substrates also accumulated in these mice. These results implicate HTRA1 and its interaction with CTRP5 in L-ORD pathology.

PRéCIS:: The diagnostic capability of peripapillary retinal volume is similar to peripapillary retinal nerve fiber layer thickness for diagnosing glaucoma, but with fewer artifacts. PURPOSE: To compare the diagnostic capability of 3-dimensional peripapillary retinal volume (RV) versus 2-dimensional peripapillary retinal nerve fiber layer (RNFL) thickness for open-angle glaucoma. PATIENTS AND METHODS: A retrospective cross-sectional analysis was conducted. A total of 180 subjects (113 open-angle glaucoma, 67 normal participants) had spectral domain optical coherence tomography volume scans and RNFL thickness measurements. Peripapillary RV values were calculated using a custom-designed program with 4 circumpapillary annuli (CA): CA1 had circle diameters of 2.5 and 3.5 mm; CA2, 3 and 4 mm; CA3, 3.5 and 4.5 mm; and CA4, 4 and 5 mm. Area under the receiver operating characteristic curves were calculated for global, quadrant, and octant regions for RV (CA1 to CA4) and RNFL thickness. Pair-wise comparisons were conducted. Artifacts rates were determined. RESULTS: Mean age was 62.7±15.4 years, and 47.8% (86/180) were male. Among RV measurements, best diagnostic performances were for the smallest 2 annuli for inferior RV (CA1: 0.964, CA2: 0.955). Of the 4 annuli, CA1 had the highest diagnostic performance. Of specific regions, the inferior RV quadrant had the highest performance across CA1 to CA4. Peripapillary RV had similar diagnostic capability compared with RNFL thickness (P>0.05). The artifact rate per B-scan for RV was 6.0%, which was significantly lower compared with 2-dimensional RNFL thickness in the same patient population (32.2%, P<0.0001). CONCLUSIONS: The diagnostic capability of RV is similar to RNFL thickness for perimetric open-angle glaucoma, but RV had fewer artifacts compared with RNFL thickness.

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: 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.

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.