SUMMARY: While Duane retraction syndrome (DRS) is relatively common, surgical management of the associated strabismus can be challenging because of the lack of abduction/adduction, the variable severity of muscle contracture, and the variety of clinical presentations. In this workshop a panel of experienced surgeons provide their perspective and practical tips on the management of strabismus in patients with DRS.

PURPOSE: In thyroid orbitopathy, surgical treatment of exophthalmos and compressive optic neuropathy is orbital decompression. Deep lateral wall decompression has been advocated alone or combined with the medial wall for a "balanced" decompression. The degree of lateral decompression is dependent on the volume of the sphenoid trigone comprising the deep lateral orbital wall. This study aims to compare the volume of the trigone in various races in men and women. METHODS: After Institutional Review Board approval, patients with normal sinus CT scans (Siemens Somatom 40-slice) were retrospectively reviewed. Inclusion criteria were men and women aged 30 to 60 years, no orbital disease or surgery, normal orbital CT scans, and self-reported race (Asian, black/African American, white). Scans were measured with imaging software (Synapse, Fujifilm USA). The superior and inferior extents of the measured trigone were the superior and inferior orbital fissures, respectively. In the axial CT plane, the areas of each slice of the right and left trigone were manually outlined with the software and volume subsequently calculated based on the slice thickness (2 mm). Comparisons between groups were made via repeated measures analysis of variance. RESULTS: One hundred twenty subjects were included, 20 from each subgroup, yielding 240 measured orbits. The overall volume of the sphenoid trigone for all groups combined was 1.53 cm (standard deviation 0.72 cm). Mean male volume was significantly larger than mean female volume (1.71 ± 0.83 cm vs. 1.35 ± 0.55 cm; p = 0.004). Average left side volume was larger than paired right side volume (1.58 ± 0.74 cm vs. 1.49 ± 0.71 cm; p = 0.02). There were no significant differences in average volumes between races (p = 0.17). CONCLUSIONS: The mean sphenoid trigone volume was larger in men than in women. There were no significant differences in volume between racial groups. The data showed significant interindividual and intraindividual variability. When analyzing these data for the purposes of orbital decompression, planning should be based on each side of each patient, as the expected degree of lateral decompression may vary greatly.

Analyses of genome-wide association study (GWAS) data have revealed that detectable genetic mosaicism involving large (>2 Mb) structural autosomal alterations occurs in a fraction of individuals. We present results for a set of 24,849 genotyped individuals (total GWAS set II [TGSII]) in whom 341 large autosomal abnormalities were observed in 168 (0.68%) individuals. Merging data from the new TGSII set with data from two prior reports (the Gene-Environment Association Studies and the total GWAS set I) generated a large dataset of 127,179 individuals; we then conducted a meta-analysis to investigate the patterns of detectable autosomal mosaicism (n = 1,315 events in 925 [0.73%] individuals). Restricting to events >2 Mb in size, we observed an increase in event frequency as event size decreased. The combined results underscore that the rate of detectable mosaicism increases with age (p value = 5.5 × 10(-31)) and is higher in men (p value = 0.002) but lower in participants of African ancestry (p value = 0.003). In a subset of 47 individuals from whom serial samples were collected up to 6 years apart, complex changes were noted over time and showed an overall increase in the proportion of mosaic cells as age increased. Our large combined sample allowed for a unique ability to characterize detectable genetic mosaicism involving large structural events and strengthens the emerging evidence of non-random erosion of the genome in the aging population.

Current limitations in technology have prevented an extensive analysis of the connections among neurons, particularly within nonmammalian organisms. We developed a transsynaptic viral tracer originally for use in mice, and then tested its utility in a broader range of organisms. By engineering the vesicular stomatitis virus (VSV) to encode a fluorophore and either the rabies virus glycoprotein (RABV-G) or its own glycoprotein (VSV-G), we created viruses that can transsynaptically label neuronal circuits in either the retrograde or anterograde direction, respectively. The vectors were investigated for their utility as polysynaptic tracers of chicken and zebrafish visual pathways. They showed patterns of connectivity consistent with previously characterized visual system connections, and revealed several potentially novel connections. Further, these vectors were shown to infect neurons in several other vertebrates, including Old and New World monkeys, seahorses, axolotls, and Xenopus. They were also shown to infect two invertebrates, Drosophila melanogaster, and the box jellyfish, Tripedalia cystophora, a species previously intractable for gene transfer, although no clear evidence of transsynaptic spread was observed in these species. These vectors provide a starting point for transsynaptic tracing in most vertebrates, and are also excellent candidates for gene transfer in organisms that have been refractory to other methods.

OBJECTIVE: To determine whether peripheral diabetic retinopathy (DR) lesions identified on ultrawide field (UWF) imaging are associated with increased DR progression. DESIGN: Prospective, longitudinal cohort. PARTICIPANTS: Two hundred eyes of 100 participants previously enrolled in a comparative instrument validation study. METHODS: Baseline mydriatic 7-standard field Early Treatment Diabetic Retinopathy Study (ETDRS) photographs and UWF images were obtained. On UWF images, DR lesions with a greater extent outside versus inside standard ETDRS fields were defined as predominantly peripheral lesions (PPLs). Follow-up ETDRS photographs were obtained 4.2±0.3 years after baseline. Baseline and follow-up DR severity were graded from ETDRS photographs. MAIN OUTCOME MEASURES: Rates of 2-step or more progression and progression to proliferative DR (PDR) in eyes with PPLs compared with eyes without PPLs identified on UWF imaging at baseline. RESULTS: In eyes without PDR (n = 109) at baseline, 56 (51%) had at least 1 field with PPLs and 43 (39%) had DR progression. Compared with eyes without PPLs, eyes with PPLs had a 3.2-fold increased risk of 2-step or more DR progression (6 [11%] vs. 19 [34%]; P = 0.005) and a 4.7-fold increased risk for progression to PDR (3 [6%] vs. 14 [25%]; P = 0.005). These findings remained statistically significant after adjusting for gender, diabetes type, diabetes duration, hemoglobin A1c (HbA1c) levels, and baseline DR severity. Increasing extent of fields with PPLs increased the risk for 2-step or more DR progression (P = 0.004) and progression to PDR (P = 0.009). CONCLUSIONS: Presence and increasing extent of PPLs were associated with increased risk of DR progression over 4 years, independent of baseline DR severity and HbA1c levels. Increasing extent of PPLs substantially increased the risk of DR progression and progression to PDR, especially with less severe DR at baseline. These findings demonstrate that detailed peripheral retinal evaluation provides important information that is necessary to assess completely the risk of DR progression.

Visual recognition takes a small fraction of a second and relies on the cascade of signals along the ventral visual stream. Given the rapid path through multiple processing steps between photoreceptors and higher visual areas, information must progress from stage to stage very quickly. This rapid progression of information suggests that fine temporal details of the neural response may be important to the brain's encoding of visual signals. We investigated how changes in the relative timing of incoming visual stimulation affect the representation of object information by recording intracranial field potentials along the human ventral visual stream while subjects recognized objects whose parts were presented with varying asynchrony. Visual responses along the ventral stream were sensitive to timing differences as small as 17 ms between parts. In particular, there was a strong dependency on the temporal order of stimulus presentation, even at short asynchronies. From these observations we infer that the neural representation of complex information in visual cortex can be modulated by rapid dynamics on scales of tens of milliseconds.

BACKGROUND: This study sought to correlate the clinical features of patients with giant cell arteritis (GCA) who present with ophthalmic symptoms and signs, with 2 specific histopathological findings-the presence of giant cells and arterial wall neoangiogenesis. The goal was to assess if these pathological features might be useful in guiding the approach to patient management. METHODS: Medical charts were retrospectively reviewed from 58 patients who underwent a temporal artery biopsy at a single institution. Detailed information was collected about the clinical presentation and course, with an emphasis on visual function. Histopathological and immunohistochemical techniques were used to examine temporal artery biopsies for evidence of inflammation. Correlations were made between the clinical data and the presence of giant cells and neoangiogenesis. RESULTS: Twenty-one (34%) biopsies were positive for inflammation consistent with GCA. Although the percentage of positive biopsies with giant cells was high, neither the presence of giant cells nor neoangiogenesis was predictive of a patient's presenting visual symptoms, severity and bilaterality of vision loss, other ophthalmic manifestations of GCA, presence of headache or jaw claudication, or erythrocyte sedimentation rate. Giant cells were more common in patients with recent weight loss. Immunohistochemistry confirmed diagnoses but did not alter the clinical course or treatment plan. CONCLUSIONS: There was no correlation between the clinical, specifically visual, features of GCA and the presence or absence of giant cells or neoangiogenesis in temporal artery biopsy specimens. Although the presence of neoangiogenesis may be important in the pathogenesis of GCA, our study showed no correlation between this finding and the clinical course.

AIM/PURPOSE OF THE STUDY: To develop a one-week storage method, without serum and xenobiotics, that would maintain cell viability, morphology, and phenotype of cultured human limbal epithelial sheets. MATERIALS AND METHODS: Human limbal explants were cultured on intact human amniotic membranes for two weeks. The sheets were stored in a hermetically sealed container at 23°C in either a serum-free medium with selected animal serum-derived compounds (Quantum 286) or a xenobiotic-free medium (Minimal Essential Medium) for 4 and 7 days. Stored and non-stored cultures were analyzed for cell viability, amniotic membrane and epithelial sheet thickness, and a panel of immunohistochemical markers for immature cells (ΔNp63α, p63, Bmi-1, C/EBP∂, ABCG2 and K19), differentiated cells (K3 and Cx43), proliferation (PCNA), and apoptosis (Caspase-3). RESULTS: The cell viability of the cultures was 98 ± 1% and remained high after storage. Mean central thickness of non-stored limbal epithelial sheets was 23 ± 3 μm, and no substantial loss of cells was observed after storage. The non-stored epithelial sheets expressed a predominantly immature phenotype with ΔNp63α positivity of more than 3% in 9 of 13 cultures. After storage, the expression of ABCG2 and C/EBP∂ was reduced for the 7 day Quantum 286-storage group; (P = 0.04), and Bmi-1 was reduced after 4 day Quantum 286-storage; (P = 0.02). No other markers varied significantly. The expression of differentiation markers was unrelated to the thickness of the epithelia and amniotic membrane, apart from ABCG2, which correlated negatively with thickness of limbal epithelia (R = -0.69, P = 0.01) and ΔNp63α, which correlated negatively with amniotic membrane thickness (R = -0.59, P = 0.03). CONCLUSION: Limbal epithelial cells cultured from explants on amniotic membrane can be stored at 23°C in both serum-free and xenobiotic-free media, with sustained cell viability, ultrastructure, and ΔNp63α-positivity after both 4 and 7 days.

PURPOSE: To update the 2008 International Classification of Corneal Dystrophies (IC3D) incorporating new clinical, histopathologic, and genetic information. METHODS: The IC3D reviewed worldwide peer-reviewed articles for new information on corneal dystrophies published between 2008 and 2014. Using this information, corneal dystrophy templates and anatomic classification were updated. New clinical, histopathologic, and confocal photographs were added. RESULTS: On the basis of revisiting the cellular origin of corneal dystrophy, a modified anatomic classification is proposed consisting of (1) epithelial and subepithelial dystrophies, (2) epithelial-stromal TGFBI dystrophies, (3) stromal dystrophies, and (4) endothelial dystrophies. Most of the dystrophy templates are updated. The entity "Epithelial recurrent erosion dystrophies" actually includes a number of potentially distinct epithelial dystrophies (Franceschetti corneal dystrophy, Dystrophia Smolandiensis, and Dystrophia Helsinglandica) but must be differentiated from dystrophies such as TGFBI-induced dystrophies, which are also often associated with recurrent epithelial erosions. The chromosome locus of Thiel-Behnke corneal dystrophy is only located on 5q31. The entity previously designated as a variant of Thiel-Behnke corneal dystrophy on chromosome 10q24 may represent a novel corneal dystrophy. Congenital hereditary endothelial dystrophy (CHED, formerly CHED2) is most likely only an autosomal recessive disorder. The so-called autosomal dominant inherited CHED (formerly CHED1) is insufficiently distinct to continue to be considered a unique corneal dystrophy. On review of almost all of the published cases, the description appeared most similar to a type of posterior polymorphous corneal dystrophy linked to the same chromosome 20 locus (PPCD1). Confocal microscopy also has emerged as a helpful tool to reveal in vivo features of several corneal dystrophies that previously required histopathologic examination to definitively diagnose. CONCLUSIONS: This revision of the IC3D classification includes an updated anatomic classification of corneal dystrophies more accurately classifying TGFBI dystrophies that affect multiple layers rather than are confined to one corneal layer. Typical histopathologic and confocal images have been added to the corneal dystrophy templates.

PURPOSE: To determine whether there is an association between response to intravitreal anti-vascular endothelial growth factor agents and genotype in patients with neovascular age-related macular degeneration. METHODS: Analysis of the current literature evaluating pharmacogenetics of treatment response in patients with neovascular age-related macular degeneration. RESULTS: Studies have demonstrated associations between various genotypes and response to intravitreal anti-vascular endothelial growth factor agents. Lower-risk genotypes of the CFH, ARMS2, HTRA1, and VEGF-A genes may be associated with improved visual outcomes. Additionally, frequency of injections may be associated with certain genotypes. CONCLUSION: Genetic background may influence an individual's response to treatment of neovascular age-related macular degeneration. Further studies to investigate biologic pathways of neovascular age-related macular degeneration and gene products that are directly involved might lead to better understanding of contribution of various genes to treatment response.

PURPOSE: To evaluate the reproducibility of central subfield thickness (CST) and volume measurements from optical coherence tomography (OCT) images obtained with Zeiss Stratus and Optovue RTVue, and formulate equations to convert these measurements from RTVue to 'equivalent' Stratus values. METHODS: Cross-sectional observational study from 309 eyes of 167 participants with diabetes and at least one eye with central-involved diabetic macular edema (DME; Stratus CST ≥ 250 μm) that underwent two replicate Stratus scans followed by two replicate RTVue scans centered on the fovea. RESULTS: The Bland-Altman coefficient of repeatability for relative change in CST (the degree of change that could be expected from measurement variability) was not significantly different on Stratus and RTVue scans (10% and 16%, respectively). The replicate Stratus CST was within 10% of the initial Stratus measurement 93% of the time; the CST conversion equation predicted a Stratus value calculated from the observed RTVue value within 10% of the observed Stratus thickness 91% of the time. Bland-Altman limit of agreement for relative change in CST between measurements observed on different machines was 23%, comparing predicted versus actual Stratus measurement. CONCLUSIONS: RTVue thickness reproducibility appears similar to Stratus. Conversion equations to transform RTVue measurements to Stratus-equivalent values within 10% of the observed Stratus RT are feasible. CST changes greater than 10% when using the same machine or 20% when switching from Stratus to RTVue, after conversion to Stratus equivalents, are likely due to a true change beyond measurement error. TRANSLATIONAL RELEVANCE: Conversion equations to translate central retinal thickness measurements between OCT instruments is critical to clinical trials.

Several groups have reported the results of clinical trials of gene augmentation therapy for Leber congenital amaurosis (LCA) because of mutations in the RPE65 gene. These studies have used subretinal injection of adeno-associated virus (AAV) vectors to deliver the human RPE65 cDNA to the retinal pigment epithelial (RPE) cells of the treated eyes. In all of the studies reported to date, this approach has been shown to be both safe and effective. The successful clinical trials of gene augmentation therapy for retinal degeneration caused by mutations in the RPE65 gene sets the stage for broad application of gene therapy to treat retinal degenerative disorders.

PurposeTo study the correlation between glaucomatous visual field (VF) defects assessed by standard automated perimetry (SAP) and peripapillary retinal nerve fiber layer (RNFL) thinning measured by spectral domain optical coherence tomography (OCT) using a modified OCT-based peripapillary RNFL structure-function map.Patients and methodsPerimetric glaucoma patients and age-matched normal control subjects were recruited from a university hospital clinic. All eyes underwent testing with the Spectralis spectral domain OCT and SAP on the same day. An OCT-based correspondence map, which correlated VF areas with peripapillary RNFL sectors was created to evaluate the relationship between glaucomatous RNFL thinning and VF loss in six nerve fiber layer bundle areas. Correlations of RNFL thinning with corresponding VF defects were examined using Spearman rank-order correlations. To demonstrate the association between localized VF defects and RNFL thickness, the theoretical curves were made according to an established log-linear model. The measured RNFL thickness values and VF defects were presented in the same scatterplot for each sector.ResultsFifty-six glaucoma patients and 85 normal subjects were included in the study. Significant association between localized VF loss and RNFL thinning was found in corresponding areas. Data from the current study fit well with established log-linear models, which compare RNFL thickness values with VF defects.ConclusionAnalysis of RNFL thinning in eyes with localized glaucomatous VF defects showed good structure-function correlation in a new OCT-based structure-function correspondence map.

Despite treatment advances, diabetic eye disease remains a leading cause of visual acuity (VA) loss worldwide. No methods to prospectively determine which patients will gain or lose vision exist, limiting individualized risk assessment and management. We investigated whether noninvasive, readily obtainable spectral domain optical coherence tomography parameters were correlated with VA in eyes with current or resolved center-involved diabetic macular edema (DME). Images were evaluated for disorganization of the retinal inner layers (DRIL), cysts, epiretinal membranes, microaneurysms, subretinal fluid, and outer layer disruption/reflectivity. DRIL affecting ≥50% of the 1-mm central retinal zone was associated with worse VA in all eyes, eyes with current edema, and eyes with resolved edema. Furthermore, early 4-month change in DRIL extent predicted VA change from baseline to 1 year. These data suggest that DRIL is a robust predictor of VA in eyes with present or previous DME and more highly correlated with VA than other widely used measures, such as retinal thickness. If further studies confirm DRIL as a predictive biomarker of future VA, physicians would gain a new tool of substantial clinical and investigative importance that could significantly change the approach to ophthalmic counseling and therapeutic management in patients with diabetes.

BACKGROUND: The purpose of this study is to describe a patient who was diagnosed with granulomatosis with polyangiitis based on conjunctival biopsy. This study is a case report and review of the literature. FINDINGS: A 48-year-old Caucasian woman presented with a 2-week history of a left eye peripheral corneal ulcer with adjacent conjunctivitis and a 4-month history of a non-resolving productive cough. Given her elevated serum perinuclear antineutrophil cytoplasmic antibody (P-ANCA) and erythrocyte sedimentation rate (ESR) levels as well as a chest computed topography (CT) that showed bilateral patchy infiltrates, suspicion of limited granulomatosis with polyangiitis with lung and ocular involvement was high. Because bronchoalveolar lavage was nondiagnostic for granulomatous disease, conjunctival biopsy was initially attempted in order to avoid a more invasive lung biopsy. The conjunctival biopsy revealed mixed subacute inflammatory mediators and vasculitis consistent with granulomatosis with polyangiitis. CONCLUSIONS: Conjunctival biopsy may be a valuable, minimally invasive method for diagnosing systemic granulomatosis with polyangiitis.

PURPOSE: To study the association between periodontal disease (PD) and age-related macular degeneration (AMD). METHODS: For this cross-sectional analysis, 8,208 adults aged 40 years or older with retinal photographs graded for AMD were used from the National Health and Nutrition Examination Survey III. National Health and Nutrition Examination Survey III standardized dental measurements of PD status (defined as loss of >3 mm of attachment between the gum and tooth in at least 10% of sites measured). Participants were stratified into 60 years or younger and older than 60 years of age groups. Association between PD and AMD was assessed while controlling for sex, race, education, poverty income ratio, smoking, hypertension, body mass index, cardiovascular disease, and C-reactive protein. RESULTS: In this population, a total of 52.30% had PD, and the prevalence of AMD was 11.45%. Logistic regression model controlled for confounders and stratified by age 60 years or younger versus older than 60 years showed PD to be independently associated with an increased risk for AMD (odds ratio = 1.96, 95% confidence interval = 1.22-3.14, P = 0.006) for those aged 60 years or younger but not for subjects older than 60 years (odds ratio = 1.32, confidence interval = 0.93-1.90, P = 0.120). CONCLUSION: In this population-based study, PD is independently associated with AMD in those aged 60 years or younger.

PURPOSE: To evaluate the efficacy of combination pars plana vitrectomy, endoscopic peripheral panretinal photocoagulation, and endocyclophotocoagulation (ECP) as compared with standard care in patients with neovascular glaucoma. METHODS: This age-matched case-controlled retrospective series of 54 eyes compared the clinical outcomes between a consecutive series of combination pars plana vitrectomy/panretinal photocoagulation/ECP (n = 27) versus the current standard of care (n = 27) for patients with neovascular glaucoma. "Standard" treatments for patients with neovascular glaucoma include panretinal photocoagulation, intravitreal bevacizumab, filtration surgery, pars plana vitrectomy, and Ahmed valve placement. RESULTS: After 1 year, mean intraocular pressure reduced from 40.7 ± 12.40 mmHg preoperatively to 12.3 ± 4.84 mmHg (P < 0.001) in the ECP group and from 34.7 ± 12.38 mmHg to 23.2 ± 12.34 mmHg in the control group (P = 0.002). Compared with controls, the mean drop in intraocular pressure in the ECP group was significantly greater at all postoperative visits. Logarithm of the minimal angle of resolution visual acuity outcomes were similar in both groups. There were 2 cases (7.4%) of postoperative phthisis bulbi in each group. CONCLUSION: Endoscopic pars plana vitrectomy, panretinal photocoagulation, and ECP seem to control intraocular pressure to a greater extent than standard glaucoma treatments in patients with neovascular glaucoma. In this aged-matched comparative case series, there was no significant difference between the two treatments' effects on visual acuity.

PURPOSE: The purpose of this study was to evaluate the outcomes of phacoemulsification in patients with ocular graft-versus-host disease (GVHD). METHODS: The occurrence of cataracts, cataract surgery, and its outcomes were analyzed in the medical records of 229 patients (458 eyes) with ocular GVHD. Outcome measures included pre- and postoperative corrected distance visual acuity (CDVA) and the rate of postoperative complications. RESULTS: Of the 458 eyes evaluated, 58 were pseudophakic; from the 400 phakic eyes, 238 (59 %) presented with cataracts and 62 (26 %) underwent cataract surgery. Analysis of postoperative complications and visual outcomes at 1 month was performed in 51 eyes in which detailed surgical and immediate postoperative records were available. Preoperatively, the mean CDVA was 0.67 ± 0.57 LogMAR (Snellen 20/93), improving postoperatively to 0.17 ± 0.18 (Snellen 20/29) at 1 month (P < 0.0001), and to 0.13 ± 0.14 (Snellen 20/26) by the final follow-up visit (P < 0.0001). Postoperative complications included corneal epithelial defects (8 %), filamentary keratitis (6 %), worsening of corneal epitheliopathy (16 %), posterior capsular opacification (18 %), and cystoid macular edema (4 %). A corrected distance visual acuity of 20/30 or better was achieved in 87 % of the eyes; suboptimal CDVA improvement was attributable to severe ocular surface disease, pre-existing advanced glaucoma, and prior macular surgery. CONCLUSIONS: Phacoemulsification in patients with chronic ocular GVHD is a safe and efficacious procedure resulting in significant visual improvement. Overall, postoperative adverse events responded well to timely management.

PURPOSE: To assess temporal summation in children with a history of retinopathy of prematurity (ROP) by determining the critical duration (tCRIT) for complete temporal summation under rod-mediated conditions. From prior ERG studies, it is known that the kinetics of activation of phototransduction are prolonged in the ROP rod photoreceptor. METHODS: Dark-adapted thresholds for detecting 10° diameter stimuli with durations from 10 to 640 ms were measured. A two-alternative, spatial, forced-choice psychophysical procedure was used. The tCRIT for complete summation was estimated in former preterm subjects with a history of severe ROP (n = 7), mild ROP (n = 23), and no ROP (n = 15). The subjects ranged in age from 10.4 to 17.6 (median 15.6) years. Age-similar term-born control subjects (n = 5) were also tested. RESULTS: Critical duration was significantly longer in subjects with a history of ROP than in subjects who never had ROP or who were born at term. Mean tCRIT in the mild ROP group [127.5 (SD = 19.9) ms] and severe group [147.6 (SD = 18.9) ms] did not differ significantly, but both were significantly longer than in former preterms who never had ROP [101.1 (SD = 16.5) ms] and in term-born controls [101.0 (SD = 19.5) ms]. CONCLUSIONS: In ROP subjects, tCRIT is significantly prolonged. This is likely due to abnormal kinetics in the rod outer segment.

As many patients with severe corneal disease are not even considered as candidates for a human graft due to their high risk of rejection, it is essential to find ways to reduce the chance of rejection. One of the options is proper matching of the cornea donor and recipient for the Human Leukocyte Antigens (HLA), a subject of much debate. Currently, patients receiving their first corneal allograft are hardly ever matched for HLA and even patients undergoing a regraft usually do not receive an HLA-matched graft. While anterior and posterior lamellar grafts are not immune to rejection, they are usually performed in low risk, non-vascularized cases. These are the cases in which the immune privilege due to the avascular status and active immune inhibition is still intact. Once broken due to infection, sensitization or trauma, rejection will occur. There is enough data to show that when proper DNA-based typing techniques are being used, even low risk perforating corneal transplantations benefit from matching for HLA Class I, and high risk cases from HLA Class I and probably Class II matching. Combining HLA class I and class II matching, or using the HLAMatchmaker could further improve the effect of HLA matching. However, new techniques could be applied to reduce the chance of rejection. Options are the local or systemic use of biologics, or gene therapy, aiming at preventing or suppressing immune responses. The goal of all these approaches should be to prevent a first rejection, as secondary grafts are usually at higher risk of complications including rejections than first grafts.