Sibel Kocabeyoglu

In Vivo Confocal Microscopic Evaluation of Corneas in Patients With Exfoliation Syndrome.

Purpose:To evaluate the corneal microstructure in patients with exfoliation syndrome (XFS) with in vivo confocal microscopy (IVCM) and to compare their results with those of healthy subjects. Material and Methods:Fifty-five corneas of patients with XFS and 55 corneas of age-matched control subjects were included in this study. Basal epithelial cell, keratocyte, endothelial cell densities, as well as sub-basal nerves were evaluated. Central corneal thickness (CCT) was measured by ultrasonic pachymeter. Results:Eyes with XFS had lower cell densities in the basal epithelium (P=0.03), posterior stroma (P⩽0.001), and endothelium (P=0.008) compared with normal eyes. The number of subbasal long nerve fibers, entire subbasal nerves, as well as nerve fiber density were found to be significantly lower in the corneas of patients with XFS (2.5±1.1 nerve/frame, 5.6±2.9 nerve/frame, and 918.9±338.5 &mgr;m/frame, respectively) as compared with those of controls (2.8±0.9 nerve/frame, 7.3±3.1 nerve/frame, and 1089.1±590.0 &mgr;m/frame, respectively, P=0.026, P=0.002, and P=0.022, respectively). There was no significant difference among eyes with XFS (537.6±36.7 &mgr;m) and control group (541.8±29.9 &mgr;m) with respect to the CCT (P=0.142). Conclusions:Subjects with XFS have subnormal endothelial, keratocyte, and subbasal nerve densities. Cornea appears to be diffusely altered in the setting of XFS even without overt deposition of exfoliation material on the corneal endothelium. IVCM may be helpful in the evaluation and follow-up of patients with XFS in assessing the impact of surgical interventions and topical antiglaucomatous medications on the corneal cell densities and subbasal nerve plexus.

The Association of Chronic Topical Prostaglandin Analog Use With Meibomian Gland Dysfunction

Purpose:To evaluate the association of long-term prostaglandin analog (PGA) use with meibomian gland dysfunction (MGD) in medically treated glaucoma patients. Materials and Methods:This was a prospective cross-sectional study conducted at a single academic setting. In total, 70 eyes of 70 patients with a medical diagnosis of glaucoma who were on long-term (>12 mo) topical hypotensive medication(s) were included. Patients were classified based on whether they were on PGA or non-PGA class of medication(s). MGD was defined based on meibomian gland terminal duct obstruction and graded between 1 and 5 based on severity. For all subjects, ocular surface disease index questionnaire, break-up time, lissamine green staining, and Schirmer test (under topical anesthesia) was administered. Student t test, Mann-Whitney U test, and &khgr;2 test was used in statistical evaluations. Forty-five age-matched healthy control subjects who were not on any topical medications were also included. Results:In total, 25 patients (35.7%) were on PGA monotherapy, 21 (30.0%) were treated with fixed or unfixed PGA combination regimens, and 24 (34.3%) were on non-PGA medications. MGD prevalence was higher in patients treated with PGA monotherapy (92.0%) compared with those receiving non-PGA therapy (58.3%) (P=0.02). Obstructive type of MGD was detected in the majority of patients treated with PGAs (95.7%). Grade 2 and 3 MGD was noted in 80.5% of patients on PGA. Patients on PGA had worse ocular surface disease index and ocular surface test results (P<0.001) compared with those of control subjects. Conclusions:Long-term administration of PGA is associated with obstructive type of MGD.

In vivo confocal microscopic characteristics of crystalline keratopathy in patients with monoclonal gammopathy: Report of two cases

In this paper, we report two cases of a 62-year-old patient presented with blurred vision and a 45-year-old male diagnosed with multiple myeloma who was referred from the Department of Oncology. Slit-lamp examination, in vivo confocal microscopy (IVCM), systemic work-up and serum protein electrophoresis were obtained. In both patients, slit-lamp findings revealed bilateral diffuse subepithelial and anterior stromal crystals and IVCM showed highly reflective deposits in the corneal epithelium and stroma. The first patient was eventually diagnosed with monoclonal gammopathy of undetermined significance following bone marrow biopsy and systemic evaluation. Unusual corneal deposits may constitute the first sign of monoclonal gammopathies. IVCM may be helpful in showing the crystalline nature of the corneal deposits and guiding the clinician to the diagnosis of gammopathies. Both ophthalmologists and oncologists should be aware that corneal deposits may herald a life-threatening hematologic disease.

Serum allergen specific immunoglobulin E levels in patients with allergic conjunctivitis.

Purpose To evaluate serum allergen specific immunoglobulin E (IgE) levels in patients with various types of allergic conjunctivitis. Methods Twenty-five patients with seasonal allergic conjunctivitis (SAC), 17 patients with perennial allergic conjunctivitis (PAC), and 10 patients with vernal conjunctivitis (VC) were included in the study Specific IgE levels to Dermatophagoides pteronyssinus (Dp), Dermatophagoides farinae (Df), mixed grass pollens, and animal epithelia were measured using Pharmacia CAP system (Pharmacia Diagnostic AB, Uppsala, Sweden). Results The percentage of subjects with specific IgE against Dp and Df was statistically higher in VC (30%) compared to PAC (5.9%) and SAC (0%) (p=0.03). Specific IgE against mixed grass pollens was found in 30% of VC and 40% of SAC, whereas 10% of VC and 8% of SAC patients were found to be hypersensitive to animal epithelia. Conclusions Allergic reaction against house dust mites and pollens was common in VC, whereas specific IgE against grass pollens was remarkable in SAC. IgE levels specific to various antigens might be measured by UNICAP system, which is a rapid and practical technology.

Ocular surface alterations in blepharospasm patients treated with botulinum toxin A injection.

Purpose To evaluate ocular surface changes secondary to periocular botulinum toxin A injection in patients with essential blepharospasm. Methods Thirteen eyes of 13 patients with essential blepharospasm who underwent periocular botulinum toxin A injection were included in this prospective study. Patients were evaluated prior to and at 2-week and 1-, 3-, and 6-month time points following injections. Ocular surface tests were carried out in the order of tear break-up time (TBUT), lissamine green (LG) staining, Schirmer I test with anesthesia, and ocular surface disease index (OSDI) questionnaire for all patients. The Friedman test with Conover post hoc method was used for statistical comparisons of values at different time points. Results The TBUT was found to be increased at 1 month after the injection (8.5 ± 2.1; p = 0.018) and decreased below baseline levels (6.4 ± 2.1) at the 6-month visit (5.7 ± 2.0; p = 0.018). None of the Schirmer test values at follow-up visits were significantly different as compared to baseline levels (11.3 ± 5.5), although the 2-week measurement (14.3 ± 5.6) was significantly higher as compared to that at the 6-month follow-up visit (9.6 ± 4.9; p = 0.034). There was also a significant decrease in LG staining scores at 2-week (0.6 ± 0.4; p = 0.012) and 1-month (0.6 ± 0.4; p = 0.012) time points compared to the baseline levels (1.1 ± 0.6). The OSDI scores improved at 2-week (5.4 ± 6.8; p<0.001), 1-month (3.2 ± 5.1; p<0.001), 3-month (2.5 ± 4.4; p<0.001), and 6-month (5.5 ± 5.4; p<0.001) time points as compared to baseline levels (11.6 ± 8.5). Conclusions Botulinum toxin A injection appears to have a positive but temporary effect on ocular surface parameters in patients with blepharospasm.

Serum vitamin D deficiency and its association with systemic disease in exfoliation syndrome.

Purpose To determine the association of serum vitamin D levels with exfoliation syndrome (XFS) and evaluate its impact on co-associated systemic diseases. Methods Forty patients with XFS and 40 control subjects without XFS were recruited for this study. Serum concentrations of 25-hydroxy vitamin D [25(OH) D] were measured by high-performance liquid chromatography. Vitamin D deficiency was defined as a serum 25(OH) D concentration of <20 ng/mL. A detailed medical history including hypertension, diabetes mellitus, ischemic heart disease, cerebrovascular stroke, autoimmune disease, and neurologic disorders such as Parkinson disease and Alzheimer disease was recorded. Student t test and chi-square test was used for statistical evaluations. Results The mean age of patients with XFS and control subjects was 69.6 ± 8.1 years (range 58–90 years) and 67.1 ± 6.3 years (range 60–86 years), respectively (p>0.05). Mean 25(OH) D levels did not differ between XFS (19.8 ± 8.3 ng/mL) and control (19.9 ± 10.3 ng/mL) groups (p = 0.978). Patients with XFS had higher prevalence of cerebrovascular (p = 0.026) and cardiovascular disease (p = 0.001). There was no association between the systemic disease status and serum vitamin D levels of patients with XFS. Conclusions Although vitamin D levels were similar between XFS and control subjects, the levels were found to be decreased in both groups. Patients with XFS had a significantly higher prevalence of cerebrovascular and cardiovascular disease as compared to controls independent of their serum 25(OH) D levels. Low vitamin D level does not appear to be linked to XFS in the studied population.

Meibomian Gland Dysfunction in Patients Receiving Long-Term Glaucoma Medications.

Purpose: The purpose of this study was to evaluate the impact of meibomian gland dysfunction (MGD) on the ocular surface of patients with medically treated glaucoma. Materials and Methods: This was a cross-sectional study in which 70 subjects with glaucoma on long-term (>1 year) topical hypotensive medications were recruited. MGD was defined as the presence of signs consistent with meibomian gland terminal duct obstruction. MGD was categorized between grades 1 and 4 and plus disease according to clinical severity. The ocular surface disease index (OSDI) questionnaire was completed at the time of enrollment. Ocular surface tests consisted of tear break-up time (BUT), ocular surface staining with lissamine green (LG), and Schirmer test with anesthesia. A Student t test, &khgr;2 test, and Mann–Whitney U test were used in statistical comparisons. Forty-five healthy control subjects with no evidence of intraocular or ocular surface disease were also included. Results: MGD was detected in 56 (80.0%) subjects with glaucoma. Forty-seven patients (67.1%) had obstructive and 9 (12.9%) had atrophic type of MGD. Of these 56 cases, 47 (83.9%) had signs consistent with mild to moderate MGD. The ocular surface test results of patients with glaucoma with MGD and without MGD were significantly worse (P < 0.001) for all parameters compared with those of healthy controls. However, there were no significant differences between ocular surface disease index scores (P = 0.912), tear break-up time (P = 0.635), lissamine green scores (P = 0.248), and Schirmer results (P = 0.991) between patients with glaucoma with MGD and without MGD. Conclusions: Mild to moderate MGD is frequently encountered in patients with medically treated glaucoma. However, the presence of MGD does not appear to have an additional detrimental effect on the ocular surface to that already induced by chronic topical medication use.

Ocular Surface Alterations and In Vivo Confocal Microscopic Features of Corneas in Patients With Newly Diagnosed Graves' Disease.

Purpose: To evaluate the ocular surface characteristics and corneal microstructure in patients with newly diagnosed Graves disease (GD) with no evidence of active thyroid eye disease (TED). Methods: Eighty eyes of 40 patients with newly diagnosed GD and 40 age-matched control subjects were recruited in this cross-sectional study. All participants underwent ocular surface tests in the order of tear break-up time (BUT), lissamine green (LG) staining, Schirmer I test with anesthesia, and ocular surface disease index (OSDI) questionnaire. Basal epithelial cell, keratocyte, and endothelial cell densities and subbasal nerves were evaluated using in vivo confocal microscopy (IVCM). Independent sample t test, &khgr;2 test, and Mann–Whitney U test were used for statistical analysis. Results: Patients with GD had higher OSDI (5.9 ± 6.6 vs. 1.7 ± 2.4, respectively, P ⩽ 0.001) and LG staining scores (0.5 ± 0.6 vs. 0.2 ± 0.4, respectively, P = 0.003), and lower BUT scores (7.3 ± 2.5 vs. 9.9 ± 1.7, respectively, P < 0.001) compared with those of control subjects. Patients with GD had lower mean basal epithelial cell density (3928 ± 657 cells/mm² vs. 4771 ± 622 cells/mm², respectively) and total subbasal nerve density (958 ± 394 cells/mm² vs. 1416 ± 744 cells/mm², respectively) and higher subbasal nerve tortuosity (2.7 ± 0.8 vs. 1.6 ± 0.6, respectively) compared with those of control subjects (P < 0.001). There was a statistically significant negative correlation between the duration of symptoms of hyperthyroidism and BUT (rho = −0.273, P = 0.014) and a positive correlation between LG staining scores (rho = 0.329, P = 0.003). A significant reduction in BUT (rho = −0.238, P = 0.003) and epithelial cell density (rho = −0.174, P = 0.029) and an increase in OSDI scores (rho = 0.328, P = 0.003) were found with increasing exophthalmometry measurements. Conclusions: Ocular surface alterations begin early in the course of Graves disease before the onset of overt TED.

In vivo confocal microscopic features of corneal pseudodendritic lesions in tyrosinemia type II.

Purpose: To report the clinical and in vivo confocal microscopic (IVCM) findings of corneal deposits in a patient with tyrosinemia type II. Methods: The pretreatment and 1-month posttreatment slit-lamp examination and IVCM findings of a patient with tyrosinemia type II are described. Results: A 12-year-old girl diagnosed with tyrosinemia type II was evaluated for photophobia and bilateral ocular discomfort of 1-year duration. The patient had been placed on topical acyclovir treatment with the diagnosis of recurrent bilateral herpetic keratitis during the previous 12 months. Slit-lamp examination revealed bilateral dendritiform epithelial lesions in the central cornea, which stained poorly with fluorescein. IVCM highlighted multiple hyperreflective linear crystalline deposits at the level of superficial epithelium. One month after discontinuation of acyclovir treatment and initiation of a protein-restricted diet therapy, improvement in the patients symptoms and regression of corneal epithelial lesions was noted. Reduction in the extent of corneal deposits was also confirmed with IVCM. Conclusions: Corneal involvement, secondary to hereditary tyrosinemia type II, is characterized by pseudodendritic epithelial lesions on slit-lamp examination and hyperreflective linear deposits in the superficial epithelium using IVCM. These lesions may regress expeditiously with a low-protein diet. IVCM may be a useful tool in the differential diagnosis of this disorder by highlighting the crystalline structures in the superficial epithelial layers and also in evaluating the response to the treatment in patients with tyrosinemia type II.

Langerhans cell histiocytosis of the caruncle

A 37‐year‐old man presented with the complaint of a small non‐tender mass growing steadily on the left caruncle for 3 months. This was a soft, reddish‐yellow tumour, occupying the whole left caruncular area without impinging on the conjunctiva. Histopathological evaluation of the excisional biopsy specimen showed that the tumour was largely composed of Langerhans cells mixed with eosinophils and mature lymphocytes. There were strong CD1a and S‐100 positivity on immunohistochemical studies. Langerhans cell histiocytosis is an exceedingly rare tumour of the caruncle in the adult and this lesion cannot be distinguished from other amelanotic lesions on clinical grounds alone. Simple excision of the lesion provided a 4‐year disease‐free period.