Keratoconus (KTCN) is non-inflammatory thinning and anterior protrusion of the cornea that results in steepening and distortion of the cornea, altered refractive error, and decreased vision. Keratoconus is a complex condition of multifactorial etiology. Both genetic and environmental factors are associated with KTCN. Evidence of genetic etiology includes familial inheritance, discordance between dizygotic twins, and association with other known genetic disorders. Several loci responsible for a familial form of KTCN have been mapped; however, no mutations in any genes have been identified for any of these loci. This article focuses on the genetic aspects. In addition, bioinformatics methods applied in KTCN gene identification process are discussed.

Primary congenital glaucoma (PCG) is an autosomal recessive disorder in children due to the abnormal development of the trabecular meshwork and the anterior chamber angle. With an onset at birth to early infancy, PCG is highly prevalent in inbred populations and consanguinity is strongly associated with the disease. Gene mapping of PCG-affected families has identified three chromosomal loci, GLC3A, GLC3B and GLC3C, of which, the CYP1B1 gene on GLC3A harbors mutations in PCG. The mutation spectra of CYP1B1 vary widely across different populations but are well structured based on geographic and haplotype backgrounds. Structural and functional studies on CYP1B1 have suggested its potential role in the development and onset of glaucomatous symptoms. A new locus (GLC3D) harboring the LTBP2 gene has been characterized in developmental glaucoma but its role in classical cases of PCG is yet to be understood. In this review, we provide insight into PCG pathogenesis and the potential role of CYP1B1 in the disease phenotype.

Our current understanding of Leber's hereditary optic neuropathy (LHON)-mitochondrial connection falls short of comprehensive. Twenty years of intensive investigation have yielded a wealth of information about mitochondria, the mitochondrial genome, the metabolism of the optic nerve and other structures, and the phenotypic variability of classic LHON. However, we still cannot completely explain how primary LHON mutations injure the optic nerve or why the optic nerve is particularly at risk. We cannot explain the incomplete penetrance or the male predominance of LHON, the typical onset in young adult life without warning, or the synchronicity of visual loss. Moreover, primary LHON mutations clearly are not present in every family with the LHON phenotype (including multigenerational maternal inheritance), and they are present in only a minority of individuals who have the LHON optic neuropathy phenotype without a family history. All lines of evidence point to abnormalities of the mitochondria as the direct or indirect cause of LHON. Therefore, the mitochondria-LHON connection needs to be revisited and examined closely. This review will attempt to do that and provide an update on various aspects of LHON.

Accurate molecular diagnosis of genetic eye diseases has proven to be of great importance because of the prognostic and therapeutic value of an accurate ascertainment of the underlying genetic mutation. Efforts continue in diagnostic laboratories to develop strategies that allow the discovery of responsible gene/mutations in the individual patient using the least number of assays and economizing on the expenses and time involved in the process. Once the ophthalmologist has made the best possible clinical diagnosis, blood samples are obtained for genetic testing. In this paper we will review the basic laboratory methods utilized to identify the chromosomal or mutational etiology of genetic diseases that affect the eye.

Pseudoexfoliation (PEX) syndrome, one of the most common causes of glaucoma, represents a complex, multifactorial, late-onset disease of worldwide significance. The etiopathogenesis involves both genetic and non-genetic factors. The PEX-specific tissue alterations are caused by a generalized fibrotic matrix process, which has been characterized as a stress-induced elastosis associated with the excessive production and abnormal cross-linking of elastic microfibrils into fibrillar PEX aggregates. The identification of lysyl oxidase-like 1 (LOXL1) as a major genetic risk factor for PEX syndrome and PEX glaucoma further supports a role of elastogenesis and elastosis in the pathophysiology of PEX, as LOXL1 is a pivotal cross-linking enzyme in elastic fiber formation and stabilization. The available data suggest that LOXL1 is markedly dysregulated depending on the stage of the fibrotic process. While transient upregulation of LOXL1 during the early stages of PEX fibrogenesis participates in the formation and aggregation of abnormal PEX fiber deposits, the decreased expression of LOXL1 during the advanced stages of the disease may affect elastin metabolism and promote elastotic processes, e.g. in the lamina cribrosa, predisposing to glaucoma development. However, in view of the low penetrance of the PEX-associated risk variants of LOXL1, other genetic and/or environmental factors must contribute to the risk of developing the PEX phenotype. Some evidence exists for the contribution of additional genes with relatively small effects, e.g. clusterin (CLU), contactin-associated protein-like 2 (CNTNAP2), apolipoprotein E (APOE), glutathione S-transferases (GSTs), and tumor necrosis factor-alpha (TNFA), in certain study populations. Several environmental conditions associated with PEX, such as oxidative stress as well as pro-fibrotic cytokines and growth factors, can regulate expression of LOXL1 and elastic proteins in vitro and may therefore act as co-modulating external factors. Ultimately, both detection and functional characterization of yet unidentified genetic and non-genetic factors may lead to the development of more precise screening tools for the risk of PEX glaucoma.

Purpose : To compare the efficacy of preoperative local injection of mitomycin C (MMC) to intraoperative application of MMC in the prevention of pterygium recurrence after surgical removal. Materials and Methods : Seventy eyes of 70 patients with primary pterygia were randomly allocated to two groups. The first group (Group A, 35 eyes) received 0.1 ml of 0.15 mg/ml of subconjunctival MMC injected into the head of the pterygium 24 h before surgical excision with the bare sclera technique. The second group (Group B 35 eyes) underwent surgical removal with the bare sclera technique with intraoperative application of MMC (0.15 mg/ml) over bare sclera for 3 min. The study was performed between March 2007 and December 2008, and follow up was performed for 1 year postoperatively. Differences between frequencies in both groups were compared by the Chi-square test or Fisher exact test. Differences between means in both groups were compared by Student's t-test. P < 0.05 was considered significant. Results : The rate of pterygium recurrence was 5.70% in Group A and 8.57% in Group B at 1 year postoperatively (P>0.05). Postoperatively, scleral thinning occurred in one eye in each group that resolved by 5 months postoperatively. No serious postoperative complications occurred in either group. Conclusion : Preoperative local injection of 0.15 mg/ml MMC is as effective as intraoperative topical application of 0.15 mg/ml MMC for preventing pterygium recurrence after surgical removal.

Purpose : To assess the changes in quality of life (QOL) of patients after treatment of their Graves' ophthalmopathy (GO). Materials and Methods : In this prospective, cross-sectional study, the GO-QOL questionnaire was completed by 67 subjects before and at least 6 months after steroid treatment (61 subjects, group 1) or optic neuropathy orbital decompression (6 subjects, group 2). Visual, psychosocial, education and counseling scores (higher score = better health), GO severity and clinical activity scores and minimal clinically important difference (MCID) were recorded and analyzed for correlation and statistical significance. A P-value <0.05 was considered statistically significant. Results : The mean age of patient enrolled in the study was 38.3 years, with 43 females (64.2%). The mean duration of thyroid dysfunction and GO were 40.1 and 26.5 months, respectively. Two treatment groups were similar for all the variables (0.06 < P < 0.9), except for higher mean age in the orbital decompression group (45.2 versus 37.7 years) (P = 0.03). Mean severity, activity, visual function and psychosocial function scores significantly improved in group 1 (steroid group) (P < 0.05, all cases). A significant improvement in clinical activity score and psychosocial scores occurred in group 2 (decompression group) (P < 0.05). MCID was achieved in two-thirds of the patients, with no significant difference between groups (P > 0.05). There was no significant effect of duration of thyroid disease and GO and severity and activity of GO on QOL scores either before or after treatment (P > 0.05, all cases). Conclusion : Steroid treatment and orbital decompression significantly improve the QOL in GO. Duration, severity and activity of GO did not have a significant impact on the QOL.

Purpose : This study was aimed at to determine the frequency of excised conjunctival lesions in a patient population treated over a 10-year period. Materials and Methods : The data of all excised conjunctival lesions with tissue diagnoses from 1998 to 2008 in the pathology department were analyzed. Results : The patient group comprised 192 conjunctival specimens; 106 (55.2%) obtained from male patients and 86 (44.8 %) from female patients. The age range was 75 years with a mean age of 27.07 ± 17 years. The most frequent excised lesions were pyogenic granulomas, which represented 30.7% (59 cases). Pigmented epithelial tumors were the second most common benign conjunctival lesions (44 cases, 22.9%). Out of these cases, compound nevus represented 86.4% (38 cases) and junctional nevus represented 6.8% (3 cases). Primary acquired melanosis and subepithelial nevus were reported in two cases (4.5%) and one case (2.3%), respectively. Cystic lesions represented 12% (23 cases). These were mostly ductal retention cysts in 16 cases (70%), occupying the fornix in eight cases. Ocular surface squamous neoplasia (OSSN) was detected in 21 cases (10.9%) significantly affecting an older age group as compared to other lesions (mean age 45.9 ± 16.7). Other less frequent lesions included papilloma (10 cases, 2.5%), dermolipoma (8 cases, 4.2%), solid dermoid (3 cases, 1.6%), hemangioma (15 cases, 7.8%), and benign reactive lymphoid hyperplasia (four cases, 2.1%). Conclusion : Benign lesions were the most frequent histologically diagnosed conjunctival lesions. The true malignant lesions were lower than what has been described in many reports. The significant proportion of precancerous OSSN can be attributed to sun exposure and ultraviolet light in Egypt.

Purpose : We describe a technique for achieving pupillary dilatation in order to manage and counteract intraoperative miosis during pediatric cataract surgery using viscoadaptive viscoelastic (sodium hyaluronate 2.3%). Materials and Methods : The technique of viscomydriasis was used in six eyes with pediatric cataracts with intraoperative pupillary miosis. Results : Pupillary dilatation was achieved and maintained in all eyes throughout cataract surgery. All the surgical steps including anterior and posterior capsulorrhexis and aspiration were performed successfully. Conclusions : Viscomydriasis is a simple and effective technique for the management of intraoperative pupillary miosis during cataract surgery in pediatric eyes.

Purpose : To evaluate the effectiveness of corneal cross-linking in improving the signs and symptoms of bullous keratopathy. Materials and Methods : This prospective non-randomized case series evaluated 20 eyes with bullous ketratopathy that underwent corneal cross-linking (C3R) with riboflavin and ultraviolet-A (UVA, 370 nm, 3 mW/cm ² ). C3R was performed for 30 min in a routine procedure after removal of epithelium. Central corneal thickness (CCT), corneal haze, visual acuity (VA), and the presence of irritating symptoms were recorded before the procedure, and at 1 week, 1 months, 3 months, and 6 months after the procedure. Results : The mean CCT was 872 ± 162 μm (range: 665-1180 μm) before the procedure. Following the procedure, CCT was 855 ± 175 μm after 1 week, 839 ± 210 μm after 1 month, 866 ± 185 μm after 3 months, and 863 ± 177 μm after 6 months (P>0.05, all visits). There was no significant improvement in VA or corneal clarity after 6 months. Improvement of the following symptoms: burning, pain, and foreign body sensation were reported after 6 months by 83.3%, 75.0%, and 66.7% of patients, respectively. Persistent epithelial defect occurred in five patients (25%) resolved with frequent lubrication and bandage contact lenses. Conclusion : The outcomes of this study indicate corneal cross-linking is not an effective treatment for bullous keratopathy with respect to VA and CCT, although it can improve irritation and discomfort.

Schnyder corneal dystrophy is a rare dominant disorder mostly reported in Western and occasionally Asian populations. This report documents the condition in an affected family from the historically isolated Arabian Peninsula. A child and her mother had central crystalline keratopathy consistent with Schnyder corneal dystrophy. Diagnostic UB1AD1 testing revealed a known point mutation (c.361C>T, p.L121F) in both individuals. Available asymptomatic family members had normal ophthalmic examinations and did not have the mutation. Blood lipid profiles for the two patients revealed mildly elevated total cholesterol and low-density lipoproteins. This report documents Schnyder corneal dystrophy on the Arabian Peninsula and further confirms its relationship with heterozygous UB1AD1 missense mutation.

A 14-year-old hyperopic female with poor vision in both eyes was evaluated for ophthalmic and systemic diseases. The patient had bilateral retinal fiber myelination and greater vision loss in the more hyperopic eye. This was a rare case of reverse Straatsma syndrome, the clinical presentation which may be accompanied with significant vision loss.

Leber's hereditary optic neuropathy (LHON) is a maternally inherited, monosymptomatic disorder, characterized by severe central vision loss and optic atrophy that most frequently affects young men. The classic LHON phenotype is associated to three mitochondrial DNA mutations, mostly homoplasmic, in the Mt-ND4, Mt-ND6, and Mt-ND1 genes, encoding for complex I subunits of the mitochondrial respiratory chain. Rare cases have been described in the literature in association with variable central nervous system involvement in a syndromic form called LHON 'plus.' In the present study, we report the case of a 16-year-old boy with the 3460/ND1 mutation who presented with epilepsy, migraine, and mental retardation as non-ophthalmic features. We also investigated his relatives who all had the 3460/ND1 mutation.

We report a patient with bilaterally symmetrical perforated corneal ulcers with formation of anterior staphyloma associated with scrofuloderma. A 22-year-old female in her third month postpartum presented with multiple perforated corneal ulcers bilaterally. There was a presence of a skin lesion that was consistent with scrofuloderma. Fine needle aspiration cytology of preauricular lymph nodes showed evidence of granulomatous inflammation consistent with tuberculosis. Corneal scraping revealed the presence of coagulase-negative Staphylococcus. She was treated with topical fortified combination antibiotics (cefazolin and tobramycin). The corneal ulcer resolved with formation of anterior staphyloma in both eyes. The patient underwent anterior staphylectomy and tectonic keratoplasty in both eyes. Eight weeks postoperatively, her visual acuity improved to 20/200 in both eyes with clear grafts. Scrofuloderma may be associated with recurrent phlyctenulosis. Multiple corneal ulcerations coupled with use of topical steroids may result in corneal perforation and formation of anterior staphyloma.

To report a case of ocular surface squamous neoplasia (OSSN) masquerading as superior limbic keratoconjunctivitis (SLK). A 62-year-old woman was referred with foreign body sensation, irritation, photophobia and decreased vision in the left eye. She was initially treated for 10 months with intermittent topical corticosteroids for a presumed diagnosis of SLK. She underwent excisional biopsy of the superior conjunctiva and was found, on histopathologic evaluation, to have OSSN with moderate to marked dysplasia. This is the first reported case of OSSN masquerading with signs and symptoms of SLK. Any ocular surface lesion refractory to standard medical treatment should raise suspicion for a malignant process and warrant further cytologic or histopathologic evaluation.

T-cell prolymphocytic leukemia (T-PLL) is a rare, highly aggressive, mature T-cell neoplasm. Ocular involvement in T-PLL is very rarely described in the literature. There are only two reports in the literature documenting conjunctival involvement in cases with T-PLL. Conjunctival involvement may be the presenting sign of the disease or rarely signifies the relapse of the disease. We present a case of a 36-year-old Saudi male patient in whom bilateral red eyes were the presenting sign of T-PLL.

Conventional lid surgery of acquired epiblepharon secondary to increased orbital volume can be result of under correction of the epiblepharon, because the increased orbital volume remains unaddressed. In this case report, we present a case of acquired epiblepharon, secondary to increased orbital volume, treated with orbital decompression.

In this retrospective report, we present two cases of unilateral Vogt-Koyanagi-Harada (VKH) disease. These patients were evaluated with clinical, ophthalmological and laboratory examinations. Their response following corticosteroid administration was evaluated. Both patients had the characteristic clinical features of VKH involving only one eye, including disc edema, choroidal striae, multiple sub retinal yellow lesions and exudative retinal detachment. These cases indicate that the clinical and angiographic features were typical of VKH disease despite the unilateral involvement.