M. Erol Turaçli

Sequence Analysis and Homology Modeling Suggest That Primary Congenital Glaucoma on 2p21 Results from Mutations Disrupting Either the Hinge Region or the Conserved Core Structures of Cytochrome P4501B1

We recently reported three truncating mutations of the cytochrome P4501B1 gene (CYP1B1) in five families with primary congenital glaucoma (PCG) linked to the GLC3A locus on chromosome 2p21. This could be the first direct evidence supporting the hypothesis that members of the cytochrome P450 superfamily may control the processes of growth and differentiation. We present a comprehensive sequence analysis of the translated regions of the CYP1B1 gene in 22 PCG families and 100 randomly selected normal individuals. Sixteen mutations and six polymorphisms were identified, illustrating an extensive allelic heterogeneity. The positions affected by these changes were evaluated by building a three-dimensional homology model of the conserved C-terminal half of CYP1B1. These mutations may interfere with heme incorporation, by affecting the hinge region and/or the conserved core structures (CCS) that determine the proper folding and heme-binding ability of P450 molecules. In contrast, all polymorphic sites were poorly conserved and located outside the CCS. Northern hybridization analysis showed strong expression of CYP1B1 in the anterior uveal tract, which is involved in secretion of the aqueous humor and in regulation of outflow facility, processes that could contribute to the elevated intraocular pressure characteristic of PCG.

Therapeutical and genetical aspects of congenital glaucomas

Therapy for congenital glaucoma is primarily surgical. We have investigated 249 cases who have undergone trabeculectomy. There was a 79% success rate as regards to control of the IOP. Vision could be saved among the patients who had applied relatively early. At the end of the follow up which was 5 years IOP remained normal in the successful group. All the patients and their families were analysed genetically by their pedigrees and caryotypes. An autosomal recessive pattern with variable penetrance was found. The majority of the patients came from families with consanguineous marriages giving a rate of 66.6%. It was suggested that the course of the disease is highly affected by and related to parental consanguinity. An early age of onset and an accelerated clinical course could be well correlated.

Evaluation of the Optic Nerve Head with the Heidelberg Retina Tomograph in Diabetes Mellitus

Background: To evaluate the optic nerve head by means of the Heidelberg retina tomograph (HRT) in patients with diabetes mellitus (DM). Methods: The study group consisted of 47 patients with DM [group 1; 29 patients without diabetic retinopathy (DR) and 18 patients with non-proliferative DR] and 50 normal subjects (group 2). All patients and controls underwent a complete ophthalmological examination, and the optic nerve head topography of both eyes was evaluated by using HRT-I. One eye of these cases was randomly selected for statistical analysis. Glycosylated haemoglobin (HbA1c) levels of all the study participants were measured. Results: The HRT parameters were similar between diabetic and control groups (p > 0.05). In group 1, in the patients with duration of diabetes ≤10 years, when compared with the patients with duration of diabetes >10 years, we did not detect any statistically significant difference between the HRT parameters (p > 0.05). There was no statistically significant correlation between HBA1c levels and rim volume (r = –0.078, p = 0.601), and mean retinal nerve fibre layer thickness (r = 0.058, p = 0.700) in DM patients. Conclusion: These results suggest that non-glaucomatous diabetic patients had no decreased neuroretinal rim when compared with non-diabetic patients.

A pilot study of the use of objective structural clinical examinations for the assessment of ophthalmology education

Purpose A pilot study was carried out to evaluate the practicality, reliability, and validity of an objective structured clinical examination (OSCE) for assessing the clinical skills and abilities of specialists in ophthalmology. Methods Ten unfolded OSCE style, criterion referenced questions were asked to nine candidates to assess their clinical skills and abilities, as opposed to subject knowledge. Candidate and assessor reactions to the examination process were monitored and analyzed using participant observation and questionnaires administered immediately after the event. Relevant statistical techniques were applied to the results. Results A total of 89% of candidates passed the examination, with the pass boundary set at 70%. Candidates revealed themselves more successful in meeting clinical skill criteria (mean 77%) than clinical ability criteria (mean 72%). Candidates, assessors, and observers all expressed the view that the OSCE pilot had been a successful way of assessing clinical skills and abilities. Conclusions OSCE style assessment is an effective and efficient means of assessing skills and abilities in clinical ophthalmology education.

Exclusion of primary congenital glaucoma (buphthalmos) from two candidate regions of chromosome arm 6p and chromosome 11

Primary congenital glaucoma (gene symbol: GLC3) is characterized by an improper development of the aqueous outflow system. The reduced outflow of fluid results in an increased intraocular pressure leading to buphthalmos, optic nerve damage, and eventual visual impairment. GLC3 is a heterogeneous condition with an estimated incidence of 1:2,500 in Middle Eastern and 1:10,000 in Western countries. In many families, GLC3 is an autosomal recessive trait with presentation of an earlier age-of-onset, high intraocular pressure, enlarged cloudy cornea, buphthalmos, and a more aggressive course. The pathogenesis of GLC3 remains elusive despite extensive histologic efforts to identify a single anatomic defect. Recent advances in positional mapping and cloning of human disorders provided an opportunity to identify chromosome locations of the GLC3 phenotype. Our laboratory is currently involved in the mapping of this condition by using a combination of candidate chromosome regions associated with the GLC3 phenotype and by a general positional mapping strategy. 16 refs., 3 tabs.

Anterior megalophthalmos with pigmentary glaucoma

PurposeTo describe the ocular findings and clinical characteristics of two sisters having anterior megalophthalmos with megalocornea and pigmentary glaucoma.Material and methodsA complete ophthalmological examination was performed.ResultsMegalocornea and transillumination defects of the irides were observed associated with deep anterior chambers in both cases. In these cases, a diagnosis of anterior megalophthalmos with pigmentary glaucoma was made.ConclusionAnterior megalophthalmos is a rare hereditary condition. The ophthalmologist should be made aware of the many ocular findings that may be associated with megalophthalmos.

Psödoeksfolyasyonlu hastalarda serum lipid düzeyleri

Amac: Psodoeksfolyatif (pex) glokomlu olgularda serum lipid seviyelerini kontrol grubu ile karsilastirmak.Gerec ve yontem: Calismaya 81 pex glokomlu hasta, 26 pex sendromlu hasta ve 67 kontrol olgusu dahil edildi. Tum olgularin serumlarinda total kolesterol, HDL-kolesterol, LDL-kolesterol, VLDL-kolesterol ve trigliserid duzeyi olculdu.Bulgular: Total kolesterol, HDL-kolesterol, LDL-kolesterol seviyeleri acisindan gruplar arasinda istatistiksel farklilik saptanmadi (p > 0.05). VLDL-kolesterol ve trigliserid duzeyi ise kontrol grubunda pex glokomlu ve pex sendromlu gruba gore belirgin olarak daha yuksekti (sirasiyla; p=0.017, p=0.010).Sonuc: Serum lipid duzeyi ve psodoeksfolyasyon arasinda bir iliski saptanmadi.

Psödoeksfolyasyonlu Türk hastalarda HLA Class I antijenleri

Amac: Turk populasyonunda psodoeksfolyasyon ile human leucocyte antigens (HLA) class I antijenleri arasindaki korelasyonu saptamak. Gerec ve Yontem: En az bir gozunde psodoeksfolyasyonu olan 76 hasta ile psodoeksfolyasyonu olmayan 100 olguda HLA class I antijenleri incelendi. Bulgular: Psodoeksfolyasyon grubunda HLA A68, B39, CW4 istatistiksel olarak daha sik saptanirken HLA A1, B7 istatistiksel olarak daha az siklikta bulundu. Psodoeksfolyasyon ve kontrol grubunda haplotip frekansi acisindan istatistiksel olarak belirgin bir fark saptanmadi. Sonuc: Farkli populasyonlar ve hasta akrabalarinda yapilacak yeni calismalar psodoeksfolyasyon ile HLA arasindaki iliskinin belirlenmesinde yardimci olacaktir

Gonioscopic Evaluation of Glaucoma Patients after Trabeculectomy

Seventy-three eyes of 65 patients with various types of glaucoma have been evaluated before and after trabeculectomy. These cases have been examined gonioscopically preoperatively and in the 1st, 3rd, and 6th months. The status of the trabeculectomy defect, and synechiae related to the area, factors predisposing to the development of synechiae, have been looked at. Peripheral anterior synechia formation was more pronounced in chronic angle closure glaucoma, exfoliative glaucoma and secondary glaucoma. The relationship between synechiae and intraocular pressure has been defined. The eyes with total peripheral anterior synechia had a lesser degree of success in lowering the intraocular pressure.