Banu Turgut Ozturk

A Truncating Mutation in SERPINB6 Is Associated with Autosomal-Recessive Nonsyndromic Sensorineural Hearing Loss

More than 270 million people worldwide have hearing loss that affects normal communication. Although astonishing progress has been made in the identification of more than 50 genes for deafness during the past decade, the majority of deafness genes are yet to be identified. In this study, we mapped a previously unknown autosomal-recessive nonsyndromic sensorineural hearing loss locus (DFNB91) to chromosome 6p25 in a consanguineous Turkish family. The degree of hearing loss was moderate to severe in affected individuals. We subsequently identified a nonsense mutation (p.E245X) in SERPINB6, which is located within the linkage interval for DFNB91 and encodes for an intracellular protease inhibitor. The p.E245X mutation cosegregated in the family as a completely penetrant autosomal-recessive trait and was absent in 300 Turkish controls. The mRNA expression of SERPINB6 was reduced and production of protein was absent in the peripheral leukocytes of homozygotes, suggesting that the hearing loss is due to loss of function of SERPINB6. We also demonstrated that SERPINB6 was expressed primarily in the inner ear hair cells. We propose that SERPINB6 plays an important role in the inner ear in the protection against leakage of lysosomal content during stress and that loss of this protection results in cell death and sensorineural hearing loss.

Comparison of intravitreal bevacizumab and ranibizumab treatment for diabetic macular edema.

AIM The aim of this study was to compare the effects of bevacizumab and ranibizumab on visual function and macular thickness in patients with diabetic macular edema (DME). METHODS The data of diabetic patients who had been treated with bevacizumab for DME were reviewed. Those patients who received 1 injection of intravitreal bevacizumab and ranibizumab with at least 6-month interval were considered for enrollment. The best-corrected visual acuity (BCVA) assesment with Early Treatment Diabetic Retinopathy Study (ETDRS) chart and central subfield macular thickness (CSMT) measurement using optical coherence tomography-3 before and after the injections were recorded as outcome measures. RESULTS The study included 29 eyes of 29 patients with a mean age of 56.18±13.07 years. The median BCVA was 59 ETDRS letters and the median CSMT was 411 μm preceeding the bevacizumab injection. At the 4th-6th week control after the injection, median BCVA increased to 61.50 ETDRS letters and the median CSMT decreased to 373 μm. This change in BCVA and CSMT was found to be statistically significant (P=0.029 and P=0.011, respectively). The mean interval between bevacizumab and ranibizumab treatment was 9.54±2.64 months. Ranibizumab treatment increased the median BCVA from 53 to 66 ETDRS letters and decreased the median CSMT from 428 μm to a level of 279 μm, which were statistically significant (P<0.001 and P<0.001, respectively). The median change in BCVA was 4.5 ETDRS letters in the bevacizumab group and 6 ETDRS letters in the ranibizumab group (P=0.58), whereas the median changes in CSMT were 41 and 100 μm after bevacizumab and ranibizumab injections, respectively (P=0.005). CONCLUSIONS Bevacizumab and ranibizumab are both effective antivascular endothelial growth factor drugs preferred in the treatment of DME. Our comparison of both therapies on the same patients suggested that the effect on BCVA was not statistically different, but ranibizumab provided more decrease in CSMT.

Comparison of the Effect of Unilateral Intravitreal Bevacizumab and Ranibizumab Injection on Diabetic Macular Edema of the Fellow Eye

PURPOSE To find out whether intravitreally administered bevacizumab and ranibizumab affect the contralateral, untreated, eyes of patients with bilateral diabetic macular edema (DME). METHODS A retrospective review of patients with bilateral DME, who were treated with intravitreal bevacizumab or ranibizumab, was performed. All enrolled patients received intravitreal 1.25 mg bevacizumab or 0.5 mg ranibizumab in the eye with more severe macular edema. As outcome measures, best-corrected visual acuity (BCVA) was assessed with the Early Treatment Diabetic Retinopathy Study chart and central foveal thickness (CFT) measurement was obtained using optical coherence tomography-3 before and at 2 and 4 weeks after injections. RESULTS The study included 55 eyes of 55 patients who received bevacizumab (group 1) and 32 eyes of 32 patients who received ranibizumab (group 2). The mean age of the 55 patients [35 female (63.6%), 20 male (36.4%)] in group 1 was 54.31±12.67 years, and the mean age of the 32 patients [20 female (62.5%), 12 male (37.5%)] in group 2 was 56.01±13.29 years. The median BCVA in the uninjected eye showed no statistically significant change at any visit after either bevacizumab or ranibizumab injection (P=0.302, P=0.582, respectively). In group 1, the median CFT in the uninjected eye was 417 μm at baseline; this was reduced to 401 μm at 2 weeks and 372 μm at 4 weeks. The change in CFT was found to be statistically significant (P=0.009). No statistically significant change was found in the median CFT of uninjected eyes of patients treated with ranibizumab (399, 403, and 407 μm before and at 2 and 4 weeks after treatment, respectively). CONCLUSIONS Compared with ranibizumab, intravitreal administration of bevacizumab resulted in a greater decrease in macular thickness in the untreated eye, in patients with bilateral DME.

Topical anesthetic abuse keratopathy: a commonly overlooked health care problem.

Purpose: To evaluate the clinical course, treatment modality, factors affecting the epithelization period, and visual outcome in patients with topical anesthetic abuse keratopathy. Methods: The medical records of 19 patients with a confirmed diagnosis of topical anesthetic abuse keratopathy were retrospectively examined; occupation, initiating event, biomicroscopic findings, treatment modality, epithelization period, and best-corrected visual acuity (BCVA) were noted. The Wilcoxon signed rank test was used to compare BCVA before and after treatment; P values <0.05 were considered statistically significant. Results: In all, 26 eyes in 19 men aged 21-44 (mean age: 31 ± 6) years were included. Initiating events included exposure to arc welding flash (8 patients), metallic foreign body injury (8 patients), and chemical injury (3 patients). On admission to hospital, 10 patients (52.6%) reported that they were using topical anesthetics. Upon admission to the hospital, 10 patients (52.6%) self reported that they were using topical anesthetics. The remaining 9 subjects were discovered to be using topical anaesthetic drops during hospitalization. Twelve patients (63.2%) were found to continue using these agents during their hospitalization. Oval corneal epithelial defect, stromal infiltrate, ring-shaped keratitis, and hypopyon were noted in 100%, 46.2%, 57.7%, and 42.3% of the eyes, respectively. Topical antibiotics (fluoroquinolones or combined fortified cephalosporins and aminoglycosides), preservative-free lubricants/autologous serum, and bandage contact lens/eye patches were used for treatment. Mean epithelization period was 19.96 ± 11.16 days (range: 6-50 days). Mean pretreatment and posttreatment BCVA was 0.12 ± 0.16 (range: 0.001-0.7) and 0.66 ± 0.30 (range: 0.0-1.0), respectively (P < 0.001). Conclusions: Ophthalmologists should be suspicious of topical anesthetic abuse keratopathy in young male manual laborers specialized in welding business and foundry work presenting with persistent epithelial defects, ring-shaped keratitis, and accompanying severe ocular pain.

Effect of altered eating habits and periods during Ramadan fasting on intraocular pressure, tear secretion, corneal and anterior chamber parameters.

PurposeTo determine whether altered eating habits and periods, especially the pre-dawn meal, during Ramadan fasting have any significant effect on intraocular pressure (IOP), tear secretion, corneal and anterior chamber parameters.MethodsIOP, basal tear secretion (BTS), reflex tear secretion (RTS), and Pentacam measurements of 31 healthy volunteers were performed at 0800 and 1600 hours during Ramadan fasting and 1 month later during non-fasting period.ResultsComparison of measurements between fasting and non-fasting periods at 0800 hours revealed significantly higher values for IOP (P=0.005), RTS (P=0.006), and BTS (P=0.014) during fasting. Conversely at 1600 hours, IOP was significantly lower during fasting (P=0.013) and no statistically significant difference was noted for RTS and BTS. IOP showed a diurnal variation of 2.45 mmHg (P<0.001) and BTS showed a 3.06 mm decrease (P=0.04) during the fasting period. No significant differences could be found in the corneal and anterior chamber parameters during fasting and non-fasting periods.ConclusionsOur results revealed that fluid loading at the pre-dawn meal during Ramadan fasting might increase the IOP and tear secretion in the early morning period and these values decrease remarkably at the end of 12 h of fasting due to dehydration.

Glucose regulation influences treatment outcome in ranibizumab treatment for diabetic macular edema

PURPOSE To evaluate the effect of glucose regulation on intravitreal ranibizumab injection for clinically significant diabetic macular edema (DME). METHODS This retrospective study enrolled 65 eyes of 65 patients with persistent DME treated with intravitreal ranibizumab injection. The main outcome measures were the change in best corrected visual acuity (BCVA), the central subfield macular thickness (CSMT) recorded with optical coherence tomography (OCT), and its correlation with the serum hemoglobin A(1c) values (HbA(1c)). RESULTS The study included 24 (36.9%) female and 41 (63.1%) male patients with a mean age of 58.90±9.45 years. The mean HbA(1c) of the enrolled patients was 8.25±1.74% (range 5.7-12.7%). The median value of BCVA at baseline examination was 20/80 (52 letters), and the median CSMT was 468 μm (range 255-964 μm). In the final control after 4-6 weeks following injection, the median value of BCVA increased to 20/50 (59.50 letters) and the median CSMT decreased to 310 μm (range 129-652 μm). This change in BCVA and macular thickness was found to be significant (P<.001 for both). There was no correlation between BCVA and the change in macular thickness (coefficient=0.04, P=.78). The serum HbA(1c) values were found to be negatively correlated with the change in CSMT (coefficient=-0.50, P<.001). CONCLUSIONS The results of intravitreal ranibizumab injection for DME demonstrated a beneficial effect on visual acuity and a decrease in CSMT which is inversely correlated with the serum HbA(1c) level.

Does lens status affect the course of early intraocular pressure and anterior chamber changes after intravitreal injection

Purpose:  This study aimed to observe changes in anterior chamber parameters and the course of intraocular pressure (IOP) after injection of 0.1 ml intravitreal triamcinolone acetonide (TA) and to determine differences between phakic and pseudophakic eyes without vitreous reflux.

Ocular Changes Associated with Topiramate

Purpose: To determine the changes in refractive error, and the cornea, anterior chamber, and retina induced by topiramate. Methods: The study included 76 eyes of 38 patients that began to use topiramate due to migraine. Following ophthalmological examination, all of the patients underwent central corneal thickness (CCT), anterior chamber volume (ACV), anterior chamber depth (ACD), and anterior chamber angle (ACA) measurement using a Scheimpflug camera, as well as macular thickness, retinal and retinal nerve fiber layer thickness (RNFLT) measurements using optical coherence tomography (OCT). These procedures were repeated 15, 30, and 90 days after the initiation of topiramate therapy. Results: The median refractive error value showed a statistically significant increase from −0.25 diopters (D) to −0.62 D at the 90th day follow-up (P < 0.001). Mean CCT was 570.56 µm before treatment and increased to 573.69 µm at the 15th day follow-up, 575.31 µm at the 30th day follow-up, and 574.56 µm at the 90th day follow-up; however, these changes were not statistically significant. Mean ACV, ACD, and ACA did not exhibit statistically significant changes. Mean retinal thickness (RT) increased during the treatment from 263.46 µm to 271.60 µm, which was not statistically significant. The initial mean RNFLT was 100.56 ± 15.36 µm and significantly increased to 110.2 ± 8.41 µm and 111.03 ± 14.59 µm at the 30th and 90th day follow-ups, respectively (P  =  0.01 and P  =  0.004, respectively). Conclusions: During the 3-month follow-up of patients using topiramate 50 mg d−1 significant myopic shift and an increase in RNFLT were observed. Further studies are warranted in order to assess the effects of topiramate when used long term and at higher doses.

Control of steroid-induced glaucoma with surgical excision of sub-Tenon triamcinolone acetonide deposits: a clinical and biochemical approach

OBJECTIVE To assess the efficacy of surgical excision of sub-Tenon triamcinolone acetonide (TA) deposits in the control of steroid-induced glaucoma. DESIGN Prospective, nonrandomized, interventional case series. PARTICIPANTS Eighteen eyes of 14 subjects with increased IOP within 6 months of sub-Tenon TA injection who did not respond to medical antiglaucomatous treatment were included in the study. METHODS Under topical anaesthesia, steroid deposits were completely excised and placed in ethyl alcohol for the determination of the TA amount using high-performance liquid chromatography. The patients were followed up for 6 months and a paired-sample t test was used to compare mean IOP before and after excision of sub-Tenon TA deposits. RESULTS The mean IOP levels before and after the sub-Tenon steroid injections were 15.9 (SD 2.9) mm Hg and 36.4 (SD 8.4) mm Hg, respectively (p < 0.001). IOP levels decreased significantly after the removal of the deposits (mean 15.3 [SD 2.1] mm Hg) (p < 0.001). Within 6 months of follow-up, all glaucoma medications were stopped in 9 subjects without further IOP increase, whereas IOP control in 5 subjects necessitated using glaucoma medications. The median TA amount was found to be 7.35 mg (range 3.3-29.68 mg). IOP decrease after the excision showed no correlation with the amount of TA (p = 0.8). CONCLUSIONS Surgical excision of the sub-Tenon steroid deposit should be considered as the primary treatment for steroid-induced glaucoma refractory to medical treatment.

Topiramate-induced acute-onset myopia and central corneal thickening: Pentacam Scheimpflug imaging findings.

Topiramate is a second-line antiepileptic drug that is also used for prophylaxis of migraine and cluster headache. The most widely recognized ocular side effect of topiramate is ciliochoroidal effusion with forward displacement of the lens– iris diaphragm and anterior chamber shallowing, resulting in acute myopia and angle-closure glaucoma. To the best of our knowledge, corneal changes have not been reported in this group of patients. We report a patient who presented with acute-onset myopia and shallowing of the anterior chamber without angle-closure glaucoma secondary to topiramate use and her follow-up with the Pentacam Scheimpflug imaging system (Oculus Inc, Lynnwood, Wash.). A 29-year-old woman with a history of migraine headache presented with blurred vision. She had used topiramate (25 mg/day) for 10 days and she experienced blurred vision in both eyes early in the morning. She was asked by her ophthalmologist to stop topiramate and was referred to our clinic. Her ophthalmic examination revealed uncorrected visual acuity of 20/200 bilaterally and her bestcorrected visual acuity (BCVA) was 20/20 in both eyes, with −8.00−1.50 × 160 in the right eye and −9.00−1.25 × 20 in the left eye. Her anterior chamber depths were strikingly shallow, especially in the left eye, with forward displacement of the lens–iris diaphragm (Fig. 1A). Although there were no visible angle structures on gonioscopy, her intraocular pressures were normal, measured as 19 mm Hg OD and 18 mm Hg OS. Her undilated fundus examination was normal but B-scan ultrasonography revealed choroidal effusion. Her baseline measurements were obtained with the Pentacam Scheimpflug imaging system (Table 1). She was warned about the symptoms of angle-closure glaucoma and sent to the referring ophthalmologist to be followed with intraocular pressure measurements on a daily basis. Three days later, anterior chamber depths were better, as were iridocorneal angles (Fig. 1B). Despite improvement in anterior chamber depth and angle parameters, there was no significant change in central corneal thickness (Table 1). At her 3-week visit, her anterior chamber parameters were normalized despite a marked decrease in central corneal thickness (Fig. 1C and Table 1). Her BCVA was 20/20 in out neurosensory detachment; a presumptive diagnosis of CSCR was offered. Despite 1 intravitreal injection of triamcinolone in 2005, the clinical and angiographic appearance had remained stable for the following 4 years, at which time he presented to our institution. In December 2006, ETDRS (Early Treatment Diabetic Retinopathy Study) visual acuity was 20/16 in the right eye and 20/50 in the left eye. Examination of the asymptomatic right eye revealed only a small PED superotemporal to the optic nerve without subretinal fluid. The left eye had a 1 disc area subfoveal serous PED with pigmentary abnormalities, without subretinal fluid, lipid, or hemorrhage. On fluorescein angiography, there was pooling of fluorescein in the serous PED with no leakage. No subretinal fluid or interstitial edema was seen on optical coherence tomography (OCT) (Fig. 1). As the patient had decreased visual function, symptomatic distortion, and excellent documentation of the longstanding nature of the PED, we recommended photodynamic therapy. A 10-minute intravenous infusion of verteporfin (6 mg/m) was followed by application of a 689 nm laser (Coherent Inc, Santa Clara, Calif.) delivering 30 J/cm for 83 seconds, with a spot size of 2600 μm to cover the entire PED. No complications ensued. Within 3 weeks of treatment, the patient noticed a marked reduction in distortion and improvement in clarity. On follow-up 6 weeks later, visual acuity had improved to 20/20 with collapse of the PED. OCT images confirmed complete absence of retinal pigment epithelium elevation and retention of normal foveal contour (Fig. 2). Only mild attenuation of retinal thickness in the inner nasal subfield was seen. Fourteen weeks after treatment, no symptoms were present, visual acuity remained at 20/20, and the clinical and OCT findings remained unchanged. Fluorescein angiography showed late staining of the retinal pigment epithelium in the region of the original PED. Despite the chronic nature of the PED, this eye had only slightly attenuated retinal thickness on OCT after resolution of the PED. Limitation in visual recovery in eyes with chronic CSCR has been attributed to atrophic neurosensory retinal changes identified on OCT that are presumed to occur from longstanding neurosensory detachment. It is possible that since this eye never had documented subretinal fluid, the retinal architecture and function were relatively preserved, allowing recovery of vision to 20/20.