A rare genotype of biallelic mosaic variants in BCOR gene causing a bilateral ocular anterior segment dysgenesis and cataracts.

Oculofaciocardiodental (OFCD) syndrome is a rare X-linked dominant syndrome characterized by the involvement of the eyes, face, teeth, and heart with variable expressivity. The syndrome is caused by loss-of-function variants in the BCOR gene located on the X chromosome. OFCD affects only females with presumed embryonic lethality among males. We report a first case of a female with biallelic mosaic variants in BCOR gene, leading to a severe ocular phenotype including anterior segment dysgenesis, cataracts, and retinal involvement. The unique condition of biallelic mosaic loss-of-function mutations leads to a variable expression of an allele with the pathogenic variant, independent of the X-Inactivation pattern. This novel mechanism of co-existent biallelic mosaicism should be suspected in unexplained severe cases of OFCD.

The effect of photographic light brightness on cup to disc ratio grading.

BACKGROUND: Digital optic disc photographs are integral to remote telehealth ophthalmology, yet no quality control standards exist for the brightness setting of the images. This study evaluated the relationship between brightness setting and cup/disc ratio (c/d) grading among glaucoma specialists. METHODS: Optic disc photographs obtained during routine examinations under anesthesia were collected to construct an image library. For each optic disc, photographs were obtained at 3 light intensity settings: dark, medium, and bright. From the image library, photograph triads (dark, medium and bright) of 50 eyes (50 patients) were used to construct the study set. Nine glaucoma specialists evaluated the c/d of the study set photographs in randomized order. The relationships between the brightness levels and the c/d grading as well as graders' years in practice and variability were evaluated. RESULTS: The c/d were graded as significantly larger in bright photographs when compared to photographs taken at the medium light intensity (0.53 vs 0.48, P < 0.001) as well as those taken at the dark setting (0.47, P < 0.001). In addition, no relationship was found between ophthalmologists' years in practice and the variability of their c/d grading (P = 0.76). CONCLUSION: Image brightness affects c/d grading of nonstereoscopic disc photographs. The brighter intensity is associated with larger c/d grading. Photograph brightness may be an important factor to consider when evaluating digital disc photographs.

Role of home monitoring with iCare ONE rebound tonometer in glaucoma patients management.

AIM: To evaluate intraocular pressure (IOP) measurements and fluctuations using the iCare ONE rebound tonometer (RT-ONE), during home monitoring, in diagnosed and suspected glaucoma patients. METHODS: A retrospective case series of consecutive patients with known glaucoma or glaucoma suspects who were followed-up and treated between January 2016 and January 2017. The study included 80 eyes of 40 patients with a mean age of 59.1±14.6y (range, 24-78). All patients have undergone 4-5d of IOP home monitoring with RT-ONE at morning, noon, afternoon, and night time. RESULTS: Baseline mean IOP, as measured in the clinic (8 a.m.-12 p.m.), was 17.4±5.1 mm Hg, compared to RT-ONE home monitoring mean IOP of 15.6±4.1 mm Hg (P=0.002). Mean IOP was significantly lower at noon, afternoon and night times compared to clinic measured IOP and morning measurements (P=0.005). IOP peak measured during home monitoring was significantly higher compared to the clinic measured IOP (21.3±5.6 mm Hg and 17.4±5.1 mm Hg, P<0.001). IOP peaks during home monitoring demonstrated a majority of 47 peaks during morning measurements, compared to 23 at noon, 19 at afternoon and only 12 at night (P<0.001). The home monitoring results led to treatment modification of 44 eyes (55%), treatment regime was insufficient for 40 (50%) eyes. CONCLUSION: Home monitoring IOP with RT-ONE can provide good assessment of mean IOP, IOP fluctuations and peaks throughout the hours of the day, which lead to an accurate treatment for glaucoma patients.

Intracameral tissue plasminogen activator in trabeculectomy: a 1-year prospective, randomized, controlled study.

PURPOSE: To evaluate the safety and the adjunctive effect of intracameral tissue plasminogen activator (tPA) in trabeculectomy for patients with primary open-angle glaucoma (POAG). METHODS: This was a prospective, randomized study consisting of patients with POAG who underwent trabeculectomy in Tel Aviv Medical Center between March 2013 and December 2014. Patients were randomly assigned to two groups: Group 1 underwent mitomycin C (MMC) trabeculectomy and group 2 underwent MMC trabeculectomy with intracameral tPA. Complete and overall success were defined as intraocular pressure (IOP) between 5 and 18 mmHg and at least 30% IOP drop without and with or without anti-glaucoma treatment, respectively. RESULTS: A total of 16 patients (seven females and nine males) were recruited, and eight patients were assigned to each group. IOP at presentation was 27 ± 5.3 mmHg and 25.3 ± 5.1 mmHg, compared to 13.7 ± 4.3 mmHg and 10.6 ± 2.0 at 12 months (p < 0.0001) for groups 1 and 2, respectively. Complete success at 12 months was achieved in 62.5% of group 1 compared to 87.5% of group 2 (p = 0.28). Overall success was achieved in 87% compared to 100% of patients at 12 months (p = 0.33). No evidence of complications attributable to tPA was found. CONCLUSIONS: Augmentation of tPA during MMC trabeculectomy may have better complete and overall success rates, compared to MMC trabeculectomy. The safety profile was similar for both groups.

Effect of brimonidine tartrate on basophil activation in glaucoma patients.

AIM: To evaluate the mechanism of which brimonidine tartrate 0.15% causes clinical hypersensitivity. METHODS: A prospective case-control study comparing 8 glaucoma patients with clinical hypersensitivity to brimonidine to a control group consisting 13 healthy volunteers. Blood samples were stimulated with brimonidine 0.15%, timolol 0.5% or brimonidine tartrate/timolol maleate 0.2%/0.5%. Premixed antibodies (CD63/FITC and aIgE/PE) were added for direct staining and whole-blood samples were lysed, fixed and analyzed by a flow cytometer. The basophil population was defined by high IgE cell expression. Degranulation was identified by the expression of the activation molecule CD63. RESULTS: Basophil activation was not significant when comparing percent of activated basophils of patients and healthy controls after exposure to brimonidine (2.58%, 2.45%, respectively, P=0.72). There was a significant suppression of basophil activation when a combination of brimonidine-timolol (0.87%) was compared to timolol (2.27%; P=0.012) and to brimonidine alone (2.58%; P=0.017). CONCLUSION: The results of our study do not support the hypothesis that brimonidine induces an immediate allergic reaction. Basophil activation was suppressed by the presence of ß-blockers in patients hypersensitive to brimonidine and in healthy individuals. This finding indicates that timolol suppress brimonidine drug reaction by a different mechanism.

Intracameral bevacizumab role in trabeculectomy: A 1-year prospective randomized controlled study.

PURPOSE: To evaluate the effect of intracameral Bevacizumab on trabeculectomy success rates. METHODS: A prospective, randomized, interventional clinical trial. Patients with primary open-angle glaucoma were randomly assigned to two groups: trabeculectomy with mitomycin C and trabeculectomy with mitomycin C and intracameral bevacizumab. Complete success is defined as an intraocular pressure (IOP) reduction of at least 30% from baseline IOP to a measured pressure of between 5 and 18 mm Hg without the use of IOP lowering medications. Qualified success is defined as same achievement of reduced IOP, but with the use of IOP lowering medications. Overall success is defined as same achievement of reduced IOP with or without the use of IOP lowering medications. RESULTS: Thirty-three patients in the mitomycin C group and 36 patients in the mitomycin C and bevacizumab group were included in final analyses. The IOP at presentation was 28.3 ± 8 and 28.4 ± 8.6 mm Hg, compared to 10.8 ± 3.4 and 12.3 ± 3.7 mm Hg at 12 months (p < 0.0001) for the mitomycin C group and the mitomycin C and bevacizumab group, respectively. Complete success at 12 months was achieved in 65% of the mitomycin C group compared to 60% of the mitomycin C and bevacizumab group (p = 0.77). Overall success was achieved in 82% compared to 80% of patients at 12 months (p = 0.78). Both groups showed a statistically significant reduction in IOP after 6 and 12 months (p ⩽ 0.001). There were no statistically significant differences in visual acuity and complications. CONCLUSION: Intracameral bevacizumab during mitomycin C trabeculectomy in patients with primary open-angle glaucoma apparently does not improve success rates. The adjuvant use of intracameral bevacizumab is therefore not justified.

Glaucomatous optic disc changes despite normal baseline intraocular pressure in a child.

PURPOSE: We describe a case of normal tension glaucoma in the setting of sickle cell disease in a 9-year-old patient with a five-year follow up. OBSERVATIONS: A 9-year-old male patient with a history of sickle cell disease presented initially at the age of 4 years for evaluation of a brief episode of nonspecific eye pain that had spontaneously resolved prior to the clinic visit. Over the course of several years, the patient was noted to have progressive optic disc cupping bilaterally, retinal nerve fiber layer thinning bilaterally, and has developed a corresponding inferior arcuate defect on automated visual field testing in the right eye, all without elevated intraocular pressures (IOP). After neuro-ophthalmic pathologies were ruled out, the patient was diagnosed with glaucoma associated with sickle cell disease and normal baseline IOP, and brimonidine therapy was initiated. CONCLUSIONS AND IMPORTANCE: To our knowledge, this is the first reported case of normal-tension glaucoma in a pediatric patient. Normal-tension glaucoma may be a consideration in the evaluation of pediatric glaucoma suspects, but remains a diagnosis of exclusion.

Effect of pupil size on biometry measurements using the IOLMaster.

PURPOSE: To evaluate the effect of pupil dilation on biometric measurements and intraocular lens power calculation using the IOLMaster (Carl Zeiss Meditec). DESIGN: Prospective, observational case series. METHODS: In this prospective study, 2 consecutive optical biometry measurements, before and after pupil dilation, were obtained using the IOLMaster on 318 eyes of 214 patients at the cataract presurgery clinic. The parameters compared were axial length, corneal power, cylinder, and the corresponding intraocular lens power, which was calculated using the Sanders-Retzlaff-Kraff/Theoretical formula. RESULTS: This study found no statistically significant difference before and after dilation in axial length (0.005 mm; P = .476), corneal power (0.001 diopters [D]; P = .933), or calculated intraocular lens power (0.011 D; P = .609). A statistically significant difference was shown in cylinder measurements before and after dilation (0.102 D; P < .001). CONCLUSIONS: This study demonstrated there is no clinically significant effect of pupil dilation on the IOLMaster measurements of axial length, corneal power, and corresponding theoretical intraocular lens power calculated using the Sanders-Retzlaff-Kraff/Theoretical formula.

Original and generic latanoprost for the treatment of glaucoma and ocular hypertension: are they really the same?

We compared the intraocular pressure (IOP)-lowering effect and safety profile of latanoprost (Xalatan) with its generic variant, Glautan (Unipharm, Tel Aviv, Israel). After 1 and 4 weeks of treatment, a randomized, prospective, cross-over comparison was carried out that included patients with open-angle glaucoma or ocular hypertension, either naïve or treated and well-controlled, who were attending the Department of Ophthalmology, Tel Aviv Medical Centre, Tel Aviv, Israel, between May 2010 and November 2012. After a 3-week washout period for the medicated subjects, the participants were randomized to 4 weeks of treatment with either Xalatan or Glautan once every evening and then, after a 3-week washout period, crossed-over to the other treatment for an additional 4 weeks. Efficacy was expressed by a change in intraocular pressure at three designated hours of the day after 1 week and 1 month of treatment, and tolerability was determined by ocular side-effects as reported by the patient in a questionnaire. A total of 19 patients (mean age at initial diagnosis 66 ± 9 years, 14 females) were enrolled, of whom 17 had bilateral open-angle glaucoma and two had unilateral disease. Both drugs lowered intraocular pressure after 1 week and 1 month (P = 0.06 and P = 0.04, respectively) of treatment. Xalatan had a tendency of greater efficacy than Glautan both after 1 week and 1 month, but the difference was not statistically significant (P = 0.69 and P = 0.34, respectively). Drug safety was similar for Xalatan or Glautan, but more ocular side-effects were reported after treatment with Glautan (21 vs 12 for Xalatan, P = 0.06).

The corneal transplant score: a simple corneal graft candidate calculator.

BACKGROUND: Shortage of corneas for transplantation has created long waiting lists in most countries. Transplant calculators are available for many organs. The purpose of this study is to describe a simple automatic scoring system for keratoplasty recipient candidates, based on several parameters that we consider most relevant for tissue allocation, and to compare the system's accuracy in predicting decisions made by a cornea specialist. METHODS: Twenty pairs of candidate data were randomly created on an electronic spreadsheet. A single priority score was computed from the data of each candidate. A cornea surgeon and the automated system then decided independently which candidate in each pair should have surgery if only a single cornea was available. RESULTS: The scoring system can calculate values between 0 (lowest priority) and 18 (highest priority) for each candidate. Average score value in our randomly created cohort was 6.35 ± 2.38 (mean ± SD), range 1.28 to 10.76. Average score difference between the candidates in each pair was 3.12 ± 2.10, range 0.08 to 8.45. The manual scoring process, although theoretical, was mentally and emotionally demanding for the surgeon. Agreement was achieved between the human decision and the calculated value in 19 of 20 pairs. Disagreement was reached in the pair with the lowest score difference (0.08). CONCLUSIONS: With worldwide donor cornea shortage, waiting for transplantation can be long. Manual sorting of priority for transplantation in a long waiting list is difficult, time-consuming and prone to error. The suggested system may help achieve a justified distribution of available tissue.

Spontaneous cerebrospinal fluid otorrhea and rhinorrhea in idiopathic intracranial hypertension patients.

BACKGROUND: Spontaneous cerebrospinal fluid (CSF) leakage may occur in patients with normal or increased intracranial pressure (ICP). We describe herein spontaneous CSF leakage as a result of chronic increased ICP in 4 patients with idiopathic intracranial hypertension (IIH). Although rhinorrhea previously has been described in IIH patients, to our knowledge this is the first report of otorrhea in these patients. METHODS: Four patients with spontaneous CSF leakage were examined between 2001 and 2011; 3 presented with rhinorrhea and 1 with otorrhea. Clinical settings and manifestations were analyzed. RESULTS: All patients were found to have IIH. Three had been diagnosed with IIH several years earlier and had been noncompliant with their medical treatment, whereas in 1 patient, CSF rhinorrhea was the presenting symptom of IIH. CONCLUSION: CSF leak is a rare complication in IIH patients. We have shown that rhinorrhea can be the presenting sign in these patients and that rhinorrhea and otorrhea can be a late sign of the disease.

The role of neuroimaging in the evaluation process of children with isolated sixth nerve palsy.

PURPOSE: The purpose of this study was to assess the role of neuroimaging in identifying the etiology of pediatric isolated sixth nerve palsy (SNP). METHODS: A retrospective cohort study was conducted of all patients younger than 18 years of age with an isolated SNP seen at our medical center between 2003 and 2011. RESULTS: Sixteen children (nine girls; mean age, 4.5 years) with isolated SNP were identified during an 8-year period. Only cases with normal optic disk appearance and otherwise normal neurological examination were included into this study. Thus, 12 other children with SNP were excluded: ten children with papilledema, one child who developed a SNP following a resection of a brain tumor, and one with hydrocephalus and a shunt malfunction. All cases of isolated SNP were unilateral (ten left eyes). The most common cause for the SNP in these children was a tumor that was found in five patients. Other etiologies encountered in decreasing frequencies were: benign recurrent SNP (in four children), postviral or vaccination (in three children), and one case each of post trauma, Chiari malformation, congenital, and undetermined. Children who were found to have a tumor (9.9 ± 5.5 years) were significantly older (P = 0.019) than children who did not have a tumor (2.1 ± 1.8 years). CONCLUSIONS: Isolated SNP can be the presentation of a brain tumor in children, and therefore, early neuroimaging of the brain is recommended, especially in older children.

The efficacy of selective laser trabeculoplasty versus argon laser trabeculoplasty in pseudophakic glaucoma patients.

INTRODUCTION: This study evaluated and compared the efficacy of selective laser trabeculoplasty (SLT) and argon laser trabeculoplasty (ALT) in terms of intraocular pressure (IOP)-lowering effects in pseudophakic patients at various time points after treatment. The primary aim was to compare the efficacy of SLT and ALT in reducing the IOP of pseudophakic glaucoma patients who recently underwent successful cataract extraction surgery. The secondary endpoint was to determine the percentage of SLT and ALT patients whose IOP was successfully reduced by at least 15% from baseline. PATIENTS AND METHODS: This study was a follow-up of a prospective randomized clinical trial. Fifty-two eyes from 52 glaucoma patients with uncontrolled IOP who had previously undergone successful phacoemulsification-assisted cataract excision surgery with intracapsular lens implantation were randomly assigned to treatment with either ALT (n = 30) or SLT (n = 22). Fifteen patients were excluded due to adverse events encountered during the study, leaving a total of 18 and 19 patients in the ALT and SLT groups, respectively. IOP measurements were carried out at scheduled intervals until 12 months post-laser treatment. RESULTS: There were no significant differences in the IOP-lowering effects between the two methods at any time point during the follow-up period. The greatest differences between the two groups were observed at 1 week posttreatment and at the 3-month time point, but neither reached a level of significance. At the final checkup, the mean IOP reduction from baseline was 3.23 mmHg in the ALT group and 4.30 mmHg in the SLT group (P = 0.269). At that visit, six (35.3%) patients in the ALT group and 15 (75%) patients in the SLT group had a reduction of ≥15% from their baseline IOP. CONCLUSION: SLT and ALT are equally effective in their IOP-lowering capabilities in new pseudophakic glaucoma patients during the first 12 months after treatment.