Successful Treatment of Corneal Opacification with Associated Thickened Epithelium by Simple Peeling: Acquired Corneal Subepithelial Hypertrophy (ACSH).

PURPOSE: To study clinical and histopathological findings of corneal opacification caused by thickened epithelium leading to reduced vision and topographical changes and to evaluate the outcome of its removal. METHODS: Twelve patients (17 eyes) with central, paracentral or peripheral corneal opacification were reviewed to obtain their visual acuity, describe their slit lamp (SL) appearance (depth, extent and density) and document their topographic changes before and after peeling of the epithelium under SL or surgical removal under the microscope. Specimens of six cases were available for histopathological examination and immunohistochemical staining. RESULTS: Most of the eye opacifications were secondary to corneal procedures in 10 [Penetrating keratoplasty (PKP) in 7 for congenital glaucoma, keratoconus or adherent leukoma - usually over graft-host junction -, Photorefractive keratectomy (PRK) in 2 and Phototherapeutic keratectomy in one], chronic inflammation following trachoma or non-specific causes (3), and herpetic scar (1). Three cases were considered to be idiopathic. All cases presented with decreased vision, astigmatism or changes in topography or refraction. Their vision, clinical symptoms and topography improved after treatment. Histopathologically, all six cases shared findings that are similar to what have been described as peripheral hypertrophic subepithelial corneal degeneration (PHSCD) rather than Salzmann's nodular degeneration. None of the cases showed inflammation or subepithelial pannus formation in the excised tissue. However, our cases did not fit into the diagnosis of PHSCD because of the location of the corneal opacification (being peripheral in 41% of the corneas, the presence of underlying primary etiologic factors in 82% of the eyes and the bilateral occurrence in 5 patients. CONCLUSIONS: Meticulous SL examination aided by corneal imaging may accurately diagnose and determine the depth of corneal opacification as a cause for reduced vision. Histopathologically, the removed tissue is similar to PHSCD, but cases differ in their clinical profile. Peeling the thickened epithelial/subepithelial tissue is curative in most patients, improves visual and clinical outcome and avoids unnecessary corneal grafting.

Clinical and molecular characterisation of Bardet-Biedl syndrome in consanguineous populations: the power of homozygosity mapping.

Bardet-Biedl syndrome (BBS) is a ciliopathy with pleiotropic effect that manifests primarily as renal insufficiency, polydactyly, retinal dystrophy and obesity. The current phenotype-genotype correlation is insufficient to predict the likely causative mutation that makes sequencing of all 14 BBS genes an often necessary but highly complicated way to identify the underlying genetic defect in affected patients. In this study, homozygosity mapping is shown as a robust approach that is highly suited for genetically heterogeneous autosomal recessive disorders in populations in which consanguinity is prevalent. This approach allowed us to quickly identify seven novel mutations in seven families with BBS. Some of these mutations would have been missed by unguided routine sequencing, which suggests that missed mutations in known BBS genes could be more common than previously thought. This study, the largest to date on Saudi BBS families, also revealed interesting phenotypic aspects of BBS, including the first report of non-syndromic retinitis pigmentosa as a novel BBS phenotype.

Fundus albipunctatus and retinitis punctata albescens in a pedigree with an R150Q mutation in RLBP1.

Fundus albipunctatus (FA; OMIM 136880) is a rare form of apparently stationary night blindness characterized by the presence of myriad symmetrical round white dots in the fundus with a greater concentration in the midperiphery. A distantly similar but distinct clinical entity, retinitis punctata albescens (RPA), is also characterized by aggregation of irregular white flecks but is progressive and evolves to generalized atrophy of the retina. We studied 4 consanguineous kindreds diagnosed with FA from Saudi Arabia. Given the substantial phenotypic variation and overlap between different flecked retinal dystrophies, we evaluated all known genes associated with such conditions by both genetic analysis and direct sequencing. In one kindred, KKESH-099, we identified a homozygous R150Q alteration in RLBP1, the gene encoding the cellular retinaldehyde binding protein, associated previously with both recessive retinitis pigmentosa (arRP) and RPA. Examination of several patients aged 3-20 years over a 9-year period presented no evidence for either RP or RPA. In contrast, clinical examination of individuals with the same mutation in their fourth and fifth decade revealed signs consistent with RPA. The data suggest that the R150Q mutation in RLBP1 may result in RPA with slow progression. More importantly, younger individuals diagnosed with the milder disorder FA thought to be stationary may evolve to a more devastating and progressive phenotype.

Sclerokeratitis: an unusual presentation of squamous cell carcinoma of the conjunctiva.

OBJECTIVE: To describe three cases of squamous cell carcinoma of the conjunctiva presenting with corneal and scleral inflammation, thinning, and perforation without any tumor formation. DESIGN: Three case reports. PARTICIPANTS: Three male subjects aged 76, 66, and 61 years. INTERVENTION: The subjects had symptoms of external ocular inflammation with focal corneal or scleral thinning and inflammation, as well as interstitial keratitis in two cases. Initial diagnosis of sclerokeratitis with limbal thinning was made in all three in addition to a pterygium in case 2. MAIN OUTCOME MEASURES: Diagnosis of the carcinoma was delayed for 2 to 24 months in two cases, whereas case 2 was diagnosed on excision of a pterygium from the involved area. RESULTS: All subjects developed intraocular extension after further scleral thinning and perforation without tumefaction. CONCLUSIONS: Squamous cell carcinoma of the conjunctiva may be seen without a distinct mass and can masquerade as sclerokeratitis, scleromalacia, or interstitial keratitis. It seems that diffuse growth with inflammation leads to thinning, necrosis, and perforation of the ocular wall with resultant intraocular spread. Squamous cell carcinoma should be considered in the differential diagnosis of corneal and scleral thinning, perforation, and inflammation of unknown cause, especially in the older male subject.

Thermodynamic analysis of human retinal acetylcholinesterase inhibition using an anti-Alzheimer's drug, tacrine, through the development of a dual substrate and temperature model.

The present study determines the energy parameters, such as the Gibb's free energy change (deltaG), enthalpy change (deltaH), heat of activation (deltaH*), entropy change (deltaS), temperature coefficient (Q10) and activation energy (Ea), of human retinal acetylcholinesterase (AChE, EC 3.1.1.7) inhibition by tacrine. The stereo-frequency collisions factor (PZ, the number of sterically and energetically favorable collisions occurring between tacrine and AChE) was also studied in this investigation. Tacrine significantly increased the value of deltaG, deltaH, deltaH*, Q10, Ea and PZ factor, and decreased the value of deltaS for AChE. Since there is no known report on the inhibition of human retinal AChE by tacrine, these results were compared with the reported values for the energy parameters of camel retinal and chicken brain AChE inhibition by an anti-cancer drug, cyclophosphamide. The uniqueness of this approach lies in the development of the 'dual substrate and dual temperature' model, which may open up a new, more efficient avenue for the study of various enzyme catalyzed reactions.

Kinetic analysis of the toxicological effect of tacrine (Cognex) on human retinal acetylcholinesterase activity.

For the first time, kinetic parameters of the effect of tacrine, an anti-cholinesterase inhibitor of therapeutic potential in Alzheimer's disease has been studied on human retinal acetyl-cholinesterase (AChE). Tacrine inhibited the AChE activity in a concentration dependent manner, the IC(50) being about 45 nM. The Michaelis-Menten constant (K(m)) for the hydrolysis of acetylthiocholine iodide was found to be 0.120 mM and this value was increased by 4-52.8% in the presence of tacrine. V(max) was observed to be 2.23 micromol/h per mg protein for the control system, while it was decreased by 14.73-56.25% in the tacrine treated systems. Dixon as well as Lineweaver-Burk plots and their secondary replots indicated that the nature of the inhibition was of the mixed type, i. e. a combination of competitive and noncompetitive inhibition. The values of K(i) and K(I) were estimated to be as 37.76 and 64.36 nM, respectively.

Exclusion of AR-CHED from the chromosome 20 region containing the PPMD and AD-CHED loci.

Congenital hereditary endothelial dystrophy (CHED) is a disorder of the corneal endothelium and has been recognized to segregate in families with both autosomal dominant (AD) and autosomal recessive (AR) modes of transmission. AD-CHED has been previously linked to the pericentric region of chromosome 20. Posterior polymorphous dystrophy (PPMD), a corneal endothelial disorder showing phenotypic overlap with CHED, has also been previously genetically mapped to this region. The genetic interval containing AD-CHED is within the larger genetic interval containing the PPMD locus. This study sought to determine whether AR-CHED segregating in a consanguineous Saudi Arabian pedigree is linked to the previously mapped and overlapping loci for AD-CHED and PPMD on the pericentric region of chromosome 20. Forty members of a consanguineous Saudi Arabian pedigree segregating AR-CHED were ascertained. Short tandem-repeat polymorphic markers from the 20 cM interval on chromosome 20 containing both the PPMD and AD-CHED loci were used to genotype these individuals. LOD score analysis of the genotype data with the MENDEL software package utilizing a model of autosomal recessive inheritance with complete penetrance showed exclusion of CHED from the entire PPMD/AD-CHED interval by utilizing overlapping intervals of LOD scores of at least -2. The results obtained demonstrate that AR-CHED is not allelic to either AD-CHED or PPMD, although it has been proposed that AD-CHED may be allelic to PPMD. Thus, there are at least two genes responsible for CHED and PPMD.

A novel locus for Leber congenital amaurosis on chromosome 14q24.

Leber congenital amaurosis (LCA) is a clinically and genetically heterogeneous autosomal recessive retinal dystrophy and the most common genetic cause of congenital visual impairment. We used a DNA pooling strategy comparing the genotypes of affected to unaffected control pools in a genome-wide search for identity-by-descent on a consanguineous Saudi Arabian LCA family. A shift to homozygosity was observed in the affected DNA pool compared with the control pool at linked markers D14S606 and D14S610. Genotyping of individual DNA samples from the entire pedigree for marker D14S74, closely linked to these loci, and several flanking markers confirmed linkage with a ZMAX=13.29 at theta=0.0. These data assign a third locus (LCA3) for LCA to chromosome 14q24. This locus and the previously identified loci are excluded for other Saudi Arabian pedigrees, both confirming that this clinical disorder is genetically heterogeneous and that additional LCA genes remain to be identified.

Heparin surface-modified intraocular lenses in patients with inactive uveitis or diabetes.

OBJECTIVE: This study aimed to determine whether heparin surface-modified (HSM) intraocular lenses (IOLs) with a hydrophilic surface would reduce cell adherence and other postoperative changes compared with the conventional polymethylmethacrylate (PMMA) IOLs in patients with either diabetes mellitus or inactive uveitis. DESIGN: The study design was a randomized, double-masked, clinical trial. PARTICIPANTS: Twenty-five patients with bilateral cataracts, 14 with inactive anterior uveitis and 11 with diabetes, with an age range of 11 to 81 years (mean, 52.8 years) participated. INTERVENTION: Bilateral cataract extraction with posterior chamber IOL implantation was measured, each patient receiving an HSM lens in one eye and a PMMA lens in the other. Pharmacia one-piece HSM and PMMA IOLs were used. Postoperative ocular changes were evaluated at regular intervals for 24 months in patients with inactive uveitis and for 6 months in patients with diabetes. Patients and physicians alike were unaware of which eye contained which lens until postoperative results were compiled. Records were kept by a study coordinator. MAIN OUTCOME MEASURES: Comparisons of posterior synechiae, IOL cellular deposits, and posterior capsular fibrosis between PMMA and HSM IOLs were measured. RESULTS: Using the chi-square test, no statistically significant difference was found between the HSM and PMMA IOLs in the number of cellular deposits found on the anterior IOL surface, the number of adhesions between the iris and IOL, or the incidence of capsular opacification. CONCLUSION: The HSM and PMMA IOLs showed similar postoperative results in patients with inactive uveitis or diabetes mellitus.

An immunohistochemical study of collagens in trachoma and vernal keratoconjunctivitis.

PURPOSE: To analyse the distribution and types of collagen in the conjunctiva of patients with trachoma and vernal keratoconjunctivitis (VKC). METHODS: Conjunctival biopsy specimens were collected from 9 patients with active trachoma, 9 patients with scarred trachoma, 6 patients with active VKC and 9 control subjects. The presence and distribution of collagen was assessed microscopically with immunohistochemical techniques and a panel of monoclonal and polyclonal antibodies directed against types I, III, IV and V collagen. RESULTS: In normal conjunctiva, the staining for types I and III collagen was localised to the substantia propria. Type IV collagen was located in the epithelial, vascular endothelial and accessory lacrimal gland basement membranes. Staining for type V collagen was absent. New type V collagen deposition close to basement membranes was noted in active trachoma, scarred trachoma and VKC. The extent of deposition of type V collagen was markedly increased in scarred trachoma when compared with active trachoma. Staining for type IV collagen showed irregularly thickened epithelial basement membrane in active trachoma, and a marked increase in basement membrane type IV collagen was noted in scarred trachoma. Immunoreactivity of types I and III collagen increased in active trachoma and decreased in scarred trachoma. VKC conjunctiva contained increased amounts of types I, III and IV collagen due to marked increase in the thickness of vascular endothelial basement membrane and very prominent deposition of types I and III collagen around stromal vessels. CONCLUSIONS: Our data indicate new type V collagen formation in the conjunctiva from patients with active trachoma, scarred trachoma and VKC. Increased deposition of types I, III and IV collagen is noted in VKC and active trachoma. Our findings suggest that increased deposition of type IV collagen and new type V collagen formation contributes to the development of conjunctival fibrosis in scarred trachoma.

Macular corneal dystrophy in Saudi Arabia: a study of 56 cases and recognition of a new immunophenotype.

PURPOSE: To determine the immunophenotype or immunophenotypes of macular corneal dystrophy in Saudi Arabia. METHODS: We studied 56 cases of macular corneal dystrophy. Tissue from 60 corneal transplant buttons was stained by the avidin-biotin complex method using an anti-keratan sulfate monoclonal antibody. The serum antigenic keratan sulfate was measured in 23 of the 56 patients, four unaffected relatives, and 13 individuals with chronic actinic keratopathy. Serum and corneal tissue were studied in 17 of the 50 affected individuals with corneal transplant material. RESULTS: Thirty-five corneas (58.3%) of 29 of 50 patients did not react with anti-keratan sulfate monoclonal antibody. The stroma and abnormal intracellular and extracellular corneal accumulations reacted with anti-keratan sulfate monoclonal antibody in seven corneas (11.7%). The stroma in the other 18 corneas (30.0%) from 15 patients did not react with the anti-keratan sulfate monoclonal antibody, but corneal fibroblasts did. Twenty-one of the 23 patients with macular corneal dystrophy had no detectable serum antigenic keratan sulfate (< 9 ng/ml); two had values of 12 and 51 ng/ml, respectively, and their corneal stroma and abnormal accumulations reacted with anti-keratan sulfate monoclonal antibody. CONCLUSIONS: We detected macular corneal dystrophy type IA, a new immunophenotype characterized by the lack of detectable antigenic keratan sulfate in the serum (< 9 ng/ml), and a corneal stroma that did not react with the keratan sulfate monoclonal antibody but in which corneal fibroblasts did react with keratan sulfate monoclonal antibody (in 15 of 50 patients).

Penetrating keratoplasty in congenital hereditary endothelial dystrophy.

PURPOSE: The purpose of the study is to determine the outcome of penetrating keratoplasty in congenital hereditary endothelial dystrophy. METHODS: Records of 40 patients (13 males, 27 females) who underwent penetrating keratoplasty (56 eyes) were reviewed. The mean age at surgery was 11.8 years (range, 2 months-35 years). The mean follow-up was 37 months (range, 6-136 months). RESULTS: In 35 (62.5%) of 56 eyes that underwent primary penetrating keratoplasty, the grafts survived. Graft survival analysis showed the probability of obtaining a clear graft is 92% at 1 year, 72% at 2 years, and 56.5% at 5 years. Graft survival was statistically better in eyes where onset of the disease is delayed (P = 0.02), if the graft donor age is between 5 and 30 years versus older than 30 years (P = 0.02), and for patients who kept follow-up appointments versus those who were delinquent (P < 0.03). Visual acuity was 20/40 in 1.9%, 20/50 to 20/80 in 18.9%, 20/100 to 20/300 in 49%, and less than 20/400 in 30.2%. The main causes of graft failure were graft rejection (six eyes) and bacterial keratitis (four eyes). CONCLUSIONS: Penetrating keratoplasty in congenital hereditary endothelial dystrophy is moderately successful, and graft survival is better in cases of delayed onset compared with that of congenital onset. Early surgical intervention is recommended to prevent development or progression of amblyopia.

Phacoemulsification at King Khaled Eye Specialist Hospital--the experience of the past.

OBJECTIVE: To study the outcome of phacoemulsification (PE) compared to standard extracapsular surgery before the introduction of state-of-the-art techniques (capsulorhexis, hydrodissection, nuclear cracking, nuclear chopping, sutureless incisions) and sophisticated equipment. STUDY DESIGN: Charts from 375 patients (453 eyes) undergoing PE between 1984 and 1989 were randomly selected and studied retrospectively. A minimum age of 35 years, and a minimum follow-up of three months were required. SETTING: A large eye hospital in the Kingdom of Saudi Arabia staffed with an international faculty of ophthalmic surgeons. PATIENTS: Patients over 35 years of age undergoing PE for immature, mature and traumatic cataract. MAIN OUTCOME MEASURES: Postoperative visual acuity, and rate or frequency of intraoperative complications. RESULTS: 66.5% achieved visual acuity of 20/40 or better, which compares favourably with the 36.5% of eyes reaching this level of visual acuity after mainly standard extracapsular cataract surgery in another study at our hospital. Posterior capsule ruptures occurred in 7.5% and vitreous loss in 5.5%. Other ocular disease (odds ratio 7.51 confidence interval 4.43-12.7) and intraoperative complications (odds ratio 2.97 confidence interval 1.38-6.42) were statistically significant predictors for final visual acuity of under 20/40 (p = < 0.001 and 0.005 respectively). CONCLUSION: The outcome of PE was better than that of standard extracapsular cataract extraction in the same setting. However, since PE appeared to be used selectively, no clear advantage compared to extracapsular cataract extraction is evident in the period before the introduction of modern state-of-the-art PE-techniques.

Recurrence of climatic droplet keratopathy. Two case reports.

Climatic droplet keratopathy (CDK) is characterized by a band-shaped pattern of subepithelial opacities and golden-yellow spherules. Recurrence of this disease in corneal grafts has not been reported. We report two cases that developed recurrence of this disease in corneal grafts done for CDK, 3 1/2 years following lamellar penetrating keratoplasty and 6 years following penetrating keratoplasty. This illustrates the possibility of this degenerative disease to recur in a few years if aetiological factors are persistently present.

Photorefractive keratectomy after radial keratotomy.

BACKGROUND: Twenty-three eyes of 22 patients remained undercorrected 5 to 49 months after radial keratotomy, either alone or in combination with transverse keratotomy. METHOD: We attempted to correct the residual myopia ranging from -1.25 to -5.75 diopters (D) (with astigmatism of 0 to 1.25 D) with photorefractive keratectomy. The mean age of patients was 26 years (range 22 to 40 years). RESULTS: After photorefractive keratectomy (follow-up 6 to 17 months) uncorrected visual acuity was equal to or better than 20/20 in 39% (9 eyes), better than 20/25 in 65% (15 eyes), and better than 20/40 in 74% (17 eyes). Spectacle-corrected visual acuity was equal or better than 20/40 in all eyes; one eye (4%) lost two lines of spectacle-corrected visual acuity. Refractive error was within +/- 0.50 D in 48% (11 eyes) and within +/- 1.00 D in 65% (15 eyes). Undercorrections of more than 1.00 D occurred in 22% (5 eyes) and overcorrections of more than 1.00 D occurred in 13% (3 eyes). No or minimal haze was present in 57% (13 eyes), mild haze in 39% (9 eyes) and moderate haze in 4% (1 eye). Final uncorrected visual acuity was better (p = 0.0002) and haze was less (p = 0.003) in the group with less than -3.00 D than in the group with greater than or equal to -3.00 D. CONCLUSION: Photorefractive keratectomy after radial keratotomy is safe but less effective and less predictable in eyes with greater than or equal to -3.00 D compared to those with less than -3.00 D.

Epithelial inclusion cysts following epikeratoplasty.

BACKGROUND: Epikeratoplasty for keratoglobus performed to tectonically support the thin globular cornea may have complications such as interface opacities. METHODS: We report the case of a patient with persistent interface opacities and epithelial cysts following epikeratoplasty for keratoglobus that were treated primarily by washouts and repeated argon laser photocoagulation. RESULTS: Interface opacities led to massive epithelial inclusion cysts. Direct removal of these cysts and placement of a new lamellar graft resulted in a favorable outcome. CONCLUSION: Massive epithelial inclusion cysts may develop in the lamellar interface after epikeratoplasty. Direct surgical removal was successful.

Bacterial keratitis following phototherapeutic keratectomy.

BACKGROUND: Phototherapeutic keratectomy (PTK) is effective in the treatment of many superficial corneal disorders. The incidence of bacterial keratitis following PTK has not been assessed in a large, prospective clinical trial. METHODS: We report three cases of bacterial keratitis that occurred in a prospective study of 258 consecutive PTK procedures at King Khaled Eye Specialist Hospital. RESULTS: Three (1.2%) of 258 eyes developed bacterial keratitis during a period of follow up ranging from 1 to 24 months. All three cases were in 183 eyes (1.6%) with a diagnosis of climatic droplet keratopathy, while no cases were observed in 75 eyes with other anterior corneal disorders. Gram-positive species (Streptococcus pneumonia in two, coagulase-negative Staphylococcus in one) were the predominant species isolated from all three cases. Two of the cases were polybacterial. The final visual outcomes ranged from 20/125 to 20/400. CONCLUSIONS: The risk of bacterial keratitis following treatment of superficial corneal disorders with PTK is low but its occurrence may adversely affect the final visual outcome.