Next generation sequencing identifies mutations in Atonal homolog 7 (ATOH7) in families with global eye developmental defects.

The atonal homolog 7 (ATOH7) gene encodes a transcription factor involved in determining the fate of retinal progenitor cells and is particularly required for optic nerve and ganglion cell development. Using a combination of autozygosity mapping and next generation sequencing, we have identified homozygous mutations in this gene, p.E49V and p.P18RfsX69, in two consanguineous families diagnosed with multiple ocular developmental defects, including severe vitreoretinal dysplasia, optic nerve hypoplasia, persistent fetal vasculature, microphthalmia, congenital cataracts, microcornea, corneal opacity and nystagmus. Most of these clinical features overlap with defects in the Norrin/ß-catenin signalling pathway that is characterized by dysgenesis of the retinal and hyaloid vasculature. Our findings document Mendelian mutations within ATOH7 and imply a role for this molecule in the development of structures at the front as well as the back of the eye. This work also provides further insights into the function of ATOH7, especially its importance in retinal vascular development and hyaloid regression.

Visual field analysis in patients with Parkinson's disease.

BACKGROUND: To evaluate visual field changes in patients with Parkinson's disease. METHODS: Standard automated perimetry of 14 patients (28 eyes) with Parkinson's disease (PD) were compared with controls. PD patients with Unified Parkinson's Disease Rating Scale (UPDRS) score below 25 were included in the study. RESULTS: Visual field indices including mean deviation (-4.69+/-2.72 vs. -1.71+/-1.30, p=0.0008), pattern standard deviation (3.94+/-1.94 vs. 2.30+/-0.41, p=0.001), and corrected pattern standard deviation (3.23+/-2.18 vs. 1.20+/-0.91, p=0.003), were significantly worse in patients with PD when compared with the control group. Bilateral glaucoma-like visual field defects were evident in six patients. CONCLUSION: Parkinson's patients had worse visual field indices suggesting a common insult in the etiopathogenesis of nerve fiber layer damages observed in glaucoma and PD.

Erythrocyte membrane anionic content and urinary glycosaminoglycan excretion in type 1 diabetes: association with retinopathy.

BACKGROUND: In diabetic nephropathy, increased excretion of glycosaminoglycans and loss of basement membrane anionic charge had been documented to be related with diabetic microalbumuniria. There was no study that studied those two factors in clinical settings with a degree of diabetic retinopathy in type 1 diabetics. METHOD: Forty subjects (aged 27.3 +/- 6.3) with type 1 diabetes with different levels of diabetic retinopathy and 30 healthy subjects (aged 29.52 +/- 8.7) were included in the study. Subjects were first divided as patients without (R0) and with (R1) retinopathy. They then were further divided into two subgroups with the help of fundus angiography as diabetic lesions demonstrable with fluorescein angiography (R1A) and early diabetic retinopathy lesions on fundus examination (R1B). Erythrocyte anionic charge (EAC) was determined by the binding of cationic dye, alcian blue, and urinary glycosaminoglycan excretion and (UGAG) was determined spectrophotometrically. RESULTS: UGAG was increased (35.74 +/- 14.01 vs 21.25 +/- 6.19 micro g/mL, 95% confidence intervals [CI], 9.01-19.96, p = 0.02) and EAC (62.14 +/- 27.17 vs. 158.53 +/- 36.98 ng alcian blue 106 per 106 RBC, 95% [CI] -111.68-81.10, p = 0.0001) was decreased significantly in diabetic patients with respect to controls. As the grade of diabetic retinopathy increased, UGAG increased and EAC decreased within subgroups of diabetic patients (p < 0.005). UGAG positively correlated (r = 0.36 and p = 0.03) and EAC negatively (r = -0.695, p = 0.0001) correlated with diabetes duration. EAC and UGAG negatively correlated (r = -0.58 and p = 0.0001) with each other in type 1 diabetics. EAC (p = 0.007) and diabetes duration (p = 0.001) were found to be the two significant factors to have diabetic retinopathy in diabetics with logistic regression analysis. CONCLUSION: Although we need more prospective and larger studies to get a direct conclusion, we found that type 1 diabetic patients with less EAC and more UGAG are more likely to have diabetic retinopathy.

Conservative treatment of isolated medial orbital wall fractures.

The decision to use surgical or nonsurgical treatment for orbital blow-out fractures is still controversial. Previously, it was advocated that all blow-out fractures should be treated surgically based on the conception that extraocular muscles were blown out and trapped in the fracture area. However, a shift to a more conservative approach occurred gradually, most likely due to the evidence of spontaneous improvement. The medical records of two patients who were diagnosed as having an isolated medial wall fracture with medial rectus muscle displacement into the ethmoid sinus, as demonstrated by computed tomography, were reviewed. Both patients showed improvement only with conservative therapy.

Tear production during the neonatal period.

PURPOSE: To measure tear secretion in term and preterm infants to assess whether tear secretion correlates with the maturity of the infants and to evaluate the changes in tear production during the neonatal period. DESIGN: Prospective, observational case series. METHODS: Ninety-six term and 22 preterm medically stable infants were studied. Post-conceptional age and birth-weight of each infant were recorded. Tear secretion was measured by the Schirmer test before (total tear secretion) and after (basal tear secretion) the instillation of topical anesthetic agent. Both eyes were tested consecutively. The initial tear measurements were performed within the first 2 days of life, and tear measurements were repeated at 2 weeks and 4 weeks after birth. RESULTS: The mean total tear production was 16.3 (+/-3.6) mm in term and 7.4 (+/-3.2) mm in preterm infants. The mean basal tear production was 7.3 (+/-3.2) mm in term and 3.5 (+/-1.3) mm in preterm infants. Total tear secretion significantly correlated with birth-weight (r, 0.42, P =.04) and post-conceptional age (r, 0.56, P =.006) in preterm infants. For term infants, total tear secretion significantly increased at 2 weeks (18.1 +/- 3.4 mm, P <.001) and 4 weeks (19.5 +/- 4.1 mm, P <.001) after birth. For preterm infants, a significant increase in total tear production was observed at the fourth week (11.5 +/- 3 mm, P <.001). CONCLUSION: Tear production in newborns depends on the maturity of the infants and increases substantially during the neonatal period. Preterm infants have reduced tear secretion compared with term infants.

Influence of serum levels of sex hormones on intraocular pressure in menopausal women.

PURPOSE: The purpose of this study was to assess the effect that changes in sex hormone levels have on intraocular pressure (IOP) in menopausal women. SUBJECTS AND METHODS: Thirty menopausal women on hormone replacement therapy and 32 menopausal women who had never received hormone replacement therapy (HRT), matched for age and duration of amenorrhea, participated in this study. Intraocular pressures were measured with Goldmann applanation tonometer. Serum levels were measured for estradiol, free testosterone, and follicle stimulating hormone (FSH). The influence of serum hormone levels on IOP was assessed by correlation analysis. RESULTS: The mean IOP of postmenopausal women receiving HRT (13.29 +/- 2.28 mm Hg) was not significantly different from that of menopausal women not receiving HRT (13.56 +/- 2.5 mm Hg, P = 0.24). Higher testosterone levels were associated with higher IOPs in women receiving HRT (r = 0.48, P = 0.02) and in those not receiving HRT (r =0.42, P = 0.003). No significant correlations were observed between IOP and serum levels of estradiol and FSH in either group. CONCLUSION: Our data provide evidence for a relation between serum testosterone levels and IOP in menopause. Higher testosterone seems to have a tendency to increase IOP in menopausal women.

Isolated abducens nerve palsy induced by vincristine therapy.

We report a 28-year-old man with non-Hodgkin's lymphoma who presented with acute onset of diplopia 3 weeks after the completion of combination chemotherapy with vincristine. He had a left esotropia with marked decrease in abduction. Magnetic resonance imaging scan of the brain showed thickening and enhancement of the left abducens nerve. Lymphomatous and other intracranial pathologies were excluded, and vincristine neurotoxicity was considered as the possible etiology of the abducens nerve palsy. His diplopia improved gradually, then completely resolved 4 weeks after the cessation of vincristine therapy. We concluded that isolated ocular muscle paresis can be the presenting sing of a toxic neuropathy associated with vincristine use.

Screening for retinopathy of prematurity in a tertiary ophthalmology department in Turkey: incidence, outcomes, and risk factors.

BACKGROUND AND OBJECTIVE: The aim of this study is to determine the incidence of retinopathy of prematurity (ROP), the number of preterm infants requiring treatment for ROP, and the factors influencing the development of ROP requiring treatment in a Turkish population. PATIENTS AND METHODS: Data on 1,252 infants who were screened for ROP in an ophthalmology department were retrospectively reviewed. Infants with a gestational age (GA) of no more than 28 weeks (n = 157) were designated group 1, those between 29 and 32 weeks (n = 572) were assigned to group 2, and those between 33 and 37 weeks (n = 523) were assigned to group 3. RESULTS: In group 1, ROP was detected in 70.0% of infants, 17.8% of whom required therapy. In group 2, ROP was detected in 41.4%, and 4.0% of those required therapy. In group 3, 18.1% were diagnosed with ROP, with 0.8% requiring treatment. CONCLUSION: Retinopathy of prematurity occurs, even among more mature infants, at a frequency that merits astute screening within parameters that reflect socioeconomic differences that appear to have an effect on the incidence.

Serum erythropoietin, insulin-like growth factor 1, and vascular endothelial growth factor in etiopathogenesis of retinopathy of prematurity.

BACKGROUND AND OBJECTIVE: The role of growth factors in the pathogenesis of retinopathy of prematurity (ROP) is known. To better understand this issue, the authors investigated vascular endothelial growth factor (VEGF), insulin-like growth factor 1 (IGF-1), and erythropoietin (EPO) levels in the cord blood of premature newborns. PATIENTS AND METHODS: IGF-1, VEGF, and EPO levels were measured in cord blood samples obtained from 93 infants less than 32 weeks of gestational age at birth, and their predictive value in the development of ROP was investigated. RESULTS: The mean birth age and mean birth weight were 32.2 ± 1.5 weeks and 1,678 ± 326 g, respectively, in infants without ROP and 29.6 ± 2.3 weeks and 1,384 ± 343 g, respectively, in infants with ROP. Multivariate logistic regression analysis showed that only the gestational age and the serum VEGF at birth were independently associated with the risk of developing ROP (P = .002, Exp[B] = 0.514, CI = 95%: 0.341-0.775; P = .028, Exp[B] = 0.999, CI = 95%: 0.997-1.00). CONCLUSION: Serum VEGF levels at birth were lower in infants who later developed ROP. This may have a predictive value for ROP and contribute to the pathogenesis, because affected infants may be more susceptible to extrauterine hyperoxic insult.

Pars Plana Vitrectomy and Intravitreal Liposomal Amphotericin B in the Treatment of Candida Endophthalmitis.

Candida endophthalmitis is a common cause of fungal endophthalmitis. A case of bilateral endogenous endophthalmitis caused by Candida albicans without candidemia in an otherwise healthy 77-year-old man was reported. The patient underwent bilateral pars plana vitrectomy and intravitreal liposomal amphotericin B injections in addition to systemic fluconazole therapy. Postoperatively, a significant decrease of inflammation and resolution of abscesses were observed in both eyes. Vision improved in the left eye but remained constant in the right eye because of secondary cataract formation. To the best of our knowledge, this is the first report on the use of liposomal amphotericin B intravitreally in a patient with bilateral endogenous candida endophthalmitis. No evidence of clinical ocular toxicity was observed with the liposomal form of amphotericin B injection.

Screening criteria for retinopathy of prematurity in developing countries.

PURPOSE: Retinopathy of prematurity (ROP) is a serious problem which potentially can lead to blindness. The objective of this study is to detect the incidence of ROP and the number of preterm babies requiring treatment for ROP in our center and to establish the screening criteria for our country. METHODS: A total of 801 babies with a gestational age less than 37 weeks were screened for ROP. Babies with a gestational age (GA) less than 32 weeks (n=348) were assigned as group 1. Babies with a GA between 32 and 34 weeks (n=335) were assigned as group 2 and between 35 and 37 weeks (n=98) were assigned as group 3. Clinical features and ROP screening results of the cases were documented. RESULTS: In group 1, ROP was detected in 176 (50.9%) babies, 41 (11.8%) of whom were treated with laser/cryotherapy. In group 2, 83 (25%) cases of ROP were detected, and 11 of them (3.1%) required therapy. In group 3, 9 (9.1%) infants were diagnosed with ROP, and none of them required treatment. Clinical factors associated with ROP in group 1 were gestational age, birthweight, duration of ventilation, duration of oxygen supplementation, sepsis, and bronchopulmonary dysplasia. CONCLUSIONS: In developing countries, the criteria for ROP screening programs should be designed according to local conditions. In our country, screening all premature babies with a gestational age less than 34 weeks or a birthweight less than 1850 g appears to be appropriate.

FACT contrast sensitivity as a diagnostic tool in glaucoma: FACT contrast sensitivity in glaucoma.

PURPOSE: To investigate spatial-contrast sensitivity (CS) assessment as a tool for diagnosis of early glaucoma in patients with good visual acuity. METHODS: In this prospective cross-sectional study we evaluated one eye of 50 patients with primary open angle or normotensive glaucoma who were newly diagnosed. All met the 0.6, or better, vision requirement. CS was measured at 1.5, 3, 6, 12, and 18 cycles per degree (cpd) spatial frequencies for one luminance level (85 cd/m2) using the functional acuity contrast test (FACT). Visual fields were evaluated using the Humphrey 750i field analyzer and the 30-2 standard full threshold program. The results from the visual acuity and CS assessments were compared with results for 20 age-matched control subjects. RESULTS: CS scores were significantly lower at all spatial frequencies for the glaucoma patients than for the control subjects. The sensitivity of CS measurements was generally around 50%. Specificity ranged between 68 and 100%. FACT CS scores of less than 22 at 12 cpd spatial frequency provided sensitivity and specificity values concomitantly exceeding 60%. CONCLUSIONS: Both the presence of a significant difference between the CS of glaucoma patients and control subjects and a high specificity of contrast sensitivity suggests that the FACT test may be used as a tool for diagnosis of patients with glaucoma, besides other methods such as short-wavelength automated perimetry (SWAP).

Short-wavelength automated perimetry in patients with migraine.

BACKGROUND: The aim was to investigate short-wavelength sensitivity deficits in patients with migraine. METHODS: Fifteen migraine and 18 age-matched healthy volunteers with normal ophthalmologic examination participated in this study. Migraine characteristics were graded by the Migraine Disability Assessment Questionnaire (MIDAS). All participants underwent SWAP (short wavelength amplitude perimetry) testing using a Humphrey field analyzer; there was a 30-2 presentation pattern. RESULTS: Short wavelength amplitude perimetry parameters for mean deviation (MD; p<0.0001) and pattern standard deviation (PSD; p<0.0001) were significantly worse in the migraine group. In the migraine group 53.3%. of eyes had glaucoma hemi-field tests (GHT) outside normal limits and 10 of these had early glaucomatous visual field loss. Statistically significant correlations were found between frequency of migraine attacks and MD (p=0.02; r=0.56) and PSD (p=0.03; r=0.41) and also between the MIDAS score and MD (p=0.03; r=0.49) and PSD (p=0.04; r=0.51). In all migraine cases with early glaucomatous visual field defect a corresponding site of the head was predominantly involved in headache (p=0.03). CONCLUSION: Some patients with severe migraine have earlier defects on SWAP suggesting a common vascular insult of glaucoma and migraine, and all migraine cases with high MIDAS scores should be further evaluated for early glaucomatous visual field defects using SWAP.

Problems with attempted chorioretinal venous anastomosis by laser for nonischemic CRVO and BRVO.

PURPOSE: To report the complications and long-term results of laser-induced chorioretinal venous anastomosis in vein occlusions. PATIENTS AND METHODS: Eight consecutive eyes, 3 with central retinal vein (CRVO) and 5 with branch retinal vein occlusion (BRVO), were observed for up to 5 years after attempted laser-induced chorioretinal venous anastomosis. RESULTS: Successful chorioretinal venous anastomoses were created in 2 (25%) eyes. Patients had severe complications, including vitreous hemorrhage, choroidal neovascular membrane, choriovitreal neovascularization, rubeosis iridis and neovascular glaucoma. CONCLUSION: The utilization of a chorioretinal venous anastomosis by laser with proposed laser settings as a therapeutic modality should be further analyzed, and a careful long-term follow-up must be done to avoid vision-threatening complications.

Colobomatous macrophthalmia with microcornea syndrome: report of a new pedigree.

Colobomatous macrophthalmia with microcornea syndrome (MIM 602499) is a very rare eye malformation. To date, only two families with a total number of eight patients have been reported. We report on 13 additional cases in a single three-generation family and describe the eye findings and quantitative parameters of corneal curvature and axial ocular dimensions. All affected relatives had bilateral involvement with typical inferonasal iris coloboma, chorioretinal coloboma, microcornea, and varying degrees of axial enlargement associated with myopia. Additional findings included flatter corneal curvatures and shallower anterior chambers. Iridocorneal angle abnormalities associated with elevation of intraocular pressure were detected in three patients. The pedigree confirms the autosomal dominant pattern of inheritance with complete penetrance.

The influence of sex hormones on ocular blood flow in women.

PURPOSE: To investigate the influence of sex hormones on ocular haemodynamics, blood flow velocities in the ophthalmic and central retinal arteries and serum levels of sex hormones were measured in pre- and postmenopausal women. METHODS: Colour Doppler imaging (CDI) was used to determine the flow velocities (peak systolic velocity [PSV] and end-diastolic velocity [EDV]) and the resistive index (RI) in the ophthalmic and central retinal arteries in 22 premenopausal and 32 postmenopausal women, who had never received hormone replacement therapy. Serum levels were measured for oestradiol, free testosterone and follicle-stimulating hormone. The CDI parameters were compared between the two groups and the influence of serum levels of oestradiol and testosterone on blood flow velocities and the resistive indices were analysed. RESULTS: After correcting for age and mean arterial blood pressure, an analysis of covariance disclosed a significantly lower EDV (p=0.02) and a significantly higher RI (p=0.01) in the central retinal artery of postmenopausal women compared with premenopausal women. Partial correlation analysis, controlling for age, revealed significant correlations between the CDI parameters and serum levels of oestradiol and testosterone. For premenopausal women, PSV (r=0.58, p=0.04) and EDV (r=0.73, p=0.006) in the ophthalmic artery correlated positively with serum oestradiol levels. The RI in the central retinal artery decreased with increasing oestradiol levels in both groups (premenopausal r= -0.40, p=0.04; postmenopausal r= -0.32, p=0.05). Peak systolic velocity in the central retinal artery correlated negatively (r= -0.49, p=0.04), whereas the RI correlated positively (r=0.53, p=0.02) with testosterone levels in the premenopausal group. Postmenopausal women with higher testosterone levels had lower EDV (r= -0.53, p=0.007) in the central retinal artery and higher RI in both vessels (ophthalmic artery r=0.48, p=0.01; central retinal artery r=0.61, p=0.002). CONCLUSION: Our data provide evidence of a relationship between serum sex hormone levels and blood flow velocities and resistive indices in retrobulbar arteries. Oestradiol appears to have beneficial effects on ocular haemodynamics, whereas testosterone may act as an antagonistic to the effects of oestrogen.