Aniridia due to a novel microdeletion affecting PAX6 regulatory enhancers: case report and review of the literature.

Aniridia is a rare congenital ocular malformation that follows an autosomal dominant mode of inheritance. Most patients carry pathogenic point mutations in the paired box 6 gene (PAX6), but some carry deletions involving the 11p13 region, encompassing partly or completely PAX6 or the region downstream. We identified a novel deletion, ~564 kb in size located about 46.5 kb downstream of PAX6 in a family with bilateral aniridia and foveal hypoplasia using array-CGH and multiplex ligation-dependent probe amplification. We also reviewall of the reported deletions downstream of PAX6 in patients with aniridia and/or other congenital malformations and define the overlapping region that leads to aniridia when deleted.

Molecular analysis of Cypriot families with aniridia reveals a novel PAX6 mutation.

The present study investigated the clinical and mutational spectrum of aniridia in a cohort of 17 affected individuals from six families from Cyprus. Each proband was initially evaluated for copy number variants at the PAX6 locus and subsequently underwent PAX6 mutation screening. Sequence analysis of FOXC1 and PITX2 was performed in patients who did not carry a PAX6 mutation. The most common clinical features in the group of aniridia patients associated with aniridia were nystagmus, cataracts and glaucoma. PAX6 pathogenic mutations were identified in five out of six families (a diagnostic yield of 84%). Previously reported pathogenic mutations in PAX6 were identified in four families, which comprise p.R203*, p.R240* and p.R317*. In addition, a novel pathogenic variant (p.E220Gfs*23) was identified in a single family. No pathogenic mutations were detected in PAX6, FOXC1 or PITX2 in the only patient with a sporadic form of aniridia­like phenotype, confirming the genetic heterogeneity associated with this disease. To the best of our knowledge this is the first report on the mutational spectrum of PAX6 in aniridia patients of Cypriot ancestry. Mutational screening of PAX6 serves a crucial role in distinguishing isolated from syndromic forms of aniridia, and it may therefore eliminate the need for renal ultrasound scan surveillance, delineate the phenotype and improve genetic counseling.

Central Serous Chorioretinopathy Associated with Desmopressin Nasal Spray: Causality or Unfortunate Association.

PURPOSE: To describe the possible association between central serous chorioretinopathy (CSCR) and desmopressin use. METHODS: The case histories of 2 middle-aged men with CSCR using desmopressin nasal spray were studied. RESULTS: The diagnosis of CSCR was made on the basis of clinical features and ancillary testing (fluorescein angiography and optical coherence tomography). Both patients were using desmopressin nasal spray for polyuria when they developed the first ocular symptoms. Both of them also had an independent risk factor for developing CSCR. CONCLUSION: We suggest that desmopressin-induced hypercortisolism might implicate the development of CSCR in some patients. A larger study on patients using desmopressin nasal spray would be beneficial to confirm the possible association between this form of therapy and the development of CSCR.

Intravitreal Aflibercept in Recalcitrant Radiation Maculopathy due to External Beam Radiotherapy for Nasopharyngeal Cancer: A First Case Report.

PURPOSE: To present the safety and efficacy of intravitreal aflibercept (Eylea) in a patient with radiation maculopathy secondary to external beam radiotherapy for nasopharyngeal cancer unresponsive to other therapeutic options. METHODS: A 73-year-old female presented with decreased visual acuity in both eyes 18 months after completing 47 external beam cycles of radiation for nasopharyngeal cancer. On presentation, her best corrected visual acuity was 6/60 in the right eye and counting fingers from 1 meter in the left eye. She received 5 bevacizumab injections in the right eye and 7 bevacizumab injections in the left eye over the last year without any improvement. A treatment with intravitreal injections of aflibercept was recommended in both eyes. RESULTS: The patient received 3 intravitreal aflibercept injections (2 mg/0.05 mL) in each eye every 4 weeks. The visual acuity improved from 6/60 to 6/12 in the right eye and from counting fingers to 6/36 in the left eye. Biomicroscopy showed less exudates, hemorrhages, and microaneurysms. Optical coherence tomography revealed reduced central retinal thickness in both eyes after 1-3 intravitreal aflibercept injections. CONCLUSION: Intravitreal aflibercept should be regarded a safe and effective treatment in patients with recalcitrant macular edema due to radiation maculopathy.

Pseudotumor Cerebri in a Child with Idiopathic Growth Hormone Insufficiency Two Months after Initiation of Recombinant Human Growth Hormone Treatment.

Purpose. To report a rare case of pseudotumor cerebri (PTC) in a child two months after receiving treatment with recombinant human growth hormone (rhGH) and to emphasize the need of close collaboration between ophthalmologists and pediatric endocrinologists in monitoring children receiving rhGH. Methods. A 12-year-old boy with congenital hypothyroidism started treatment with rhGH on a dose of 1,5 mg/daily IM (4.5 IU daily). Eight weeks later, he was complaining of severe headache without any other accompanying symptoms. The child was further investigated with computed tomography scan and lumbar puncture. Results. Computed tomography scan showed normal ventricular size and lumbar puncture revealed an elevated opening pressure of 360 mm H2O. RhGH was discontinued and acetazolamide 250 mg per os twice daily was initiated. Eight weeks later, the papilledema was resolved. Conclusions. There appears to be a causal relationship between the initiation of treatment with rhGH and the development of PTC. All children receiving rhGH should have a complete ophthalmological examination if they report headache or visual disturbances shortly after the treatment. Discontinuation of rhGH and initiation of treatment with acetazolamide may be needed and regular follow-up examinations by an ophthalmologist should be recommended.

Clinical, anatomical, and electrophysiological assessments of the central retina following intravitreal bevacizumab for macular edema secondary to retinal vein occlusion.

The purpose of this study is to evaluate the long-term visual, anatomical and electrophysiological outcomes of repeated intravitreal injections of bevacizumab for macular edema due to retinal vein occlusion (RVO) and investigate any possible toxic effects on the central fovea. This is a prospective, noncomparative, interventional case series. Thirty-three eyes of 33 patients with macular edema secondary to RVO were treated with 1.25 mg/0.05 ml intravitreal bevacizumab. Nine patients had nonischemic central retinal vein occlusion (CRVO) and 24 patients had branch retinal vein occlusion (BRVO). The main outcome measures were best-corrected visual acuity, central retinal thickness (CRT), and multifocal electroretinography (mfERG) responses changes at baseline, 1 month after the third injection and at the end of the 2-year long follow-up period. Patients with CRVO had mean best-corrected Snellen visual acuity of 0.10 at baseline, which improved significantly to 0.31 after 2 years (P = 0. 028).The mean CRT at presentation was 756.28 µm and reduced significantly to 439.14 µm after 2 years (P = 0.05). Patients with BRVO had mean best-corrected Snellen visual acuity of 0.19 at baseline, which improved significantly to 0.40 after 2 years (P < 0.001). The mean CRT at presentation was 681.04 µm and reduced significantly to 369.81 µm after 2 years (P < 0.001). Mean mfERG responses within central 10° (ring1, ring2) showed statistically significant differences on P1 parameters in terms of response density and implicit time after 2 years in both CRVO and BRVO patients. Repeated intravitreal bevacizumab injections for macular edema due to either CRVO or BRVO resulted in long-term improvement of visual acuity, a reduction in CRT and statistically significant changes in the mfERG responses with nondemonstrable toxic effects on the central fovea.

Novel GLI3 mutation in a Greek-Cypriot patient with Greig cephalopolysyndactyly syndrome.

Greig cephalopolysyndactyly syndrome (GCPS) is typically characterized by preaxial or mixed preaxial and postaxial polydactyly with or without syndactyly and craniofacial features including hypertelorism and macrocephaly. Although GLI3 shows considerable pleiotropy, it is the only gene known to cause this particular phenotype. We report on a patient with GCPS caused by a novel GLI3 mutation. In addition, the patient had asymmetry of the calf muscles, most likely secondary to chronic hypertrophic radiculopathy. The GLI3 mutation identified by targeted Sanger sequencing analysis in our patient is predicted to lead to premature termination of translation. This is the first report of a Cypriot patient with a GCPS because of a novel GLI3 mutation. The report provides additional evidence in support of the rich variability in phenotypic expression, the mutational heterogeneity and ethnic diversity associated with this rare condition.

Keratoconjunctivitis and Periorbital Edema due to Ecballium elaterium.

PURPOSE: To report on a case of keratoconjunctivitis with periorbital edema after accidental exposure to undiluted juice of Ecballium elaterium fruit during the ripening season of this plant. METHODS: Case report. RESULTS: Keratoconjunctivitis with Descemet's membrane folds and superficial upper corneal well-defined edematous areas were noted after an Ecballium elaterium fruit burst and its juice splashed into the patient's left eye. Prompt administration of antibiotic and steroid eye drops along with per os antihistamine therapy, resulted in quick regression of symptoms. CONCLUSIONS: This report demonstrates the toxic effects of this herb to the eye and also that prompt therapy is effective.

Ulnar neuropathy as a complication of retinal detachment surgery and face-down positioning.

PURPOSE: To report a case of bilateral ulnar neuropathy as an extraocular complication following retinal detachment surgery and face-down positioning. METHODS: Case report. RESULTS: Bilateral hypoesthesia and numbness of the 4th and 5th finger started 2 weeks after vitrectomy for retinal detachment and face-down positioning. Due to progressive symptoms 6 months later, unilateral ulnar nerve decompression at the elbow was performed. CONCLUSIONS: This case report demonstrates that strict face-down positioning bears the risk of ulnar neuropathy.

Sustained ocular hypertension following intravitreal injections of 0.5 mg/0.05 ml ranibizumab.

To report three cases with sustained ocular hypertension following intravitreal injections of 0.5 mg/0.05 ml ranibizumab and to underline the importance of monitoring intraocular pressure (IOP) following intravitreal injections of ranibizumab (Lucentis). Three patients were found to have high IOP after intravitreal injections of 0.5 mg/0.05 ml ranibizumab. IOP was elevated after the second ranibizumab injection in patients 1 and 2, and after the third injection in patient 3. The increase in IOP was sustained, requiring treatment with anti-glaucoma eye drops in all patients, the addition of systemic carbonic anhydrase inhibitor in one patient, and the application of selective laser trabeculoplasty (SLT) in another patient. None of the patients had a previous history of glaucoma or ocular hypertension. Sustained ocular hypertension may occur after intravitreal injections of 0.5 mg/0.05 ml ranibizumab. Although the precise mechanism of the pressure rise is unknown, three eyes in our series were controlled with topical or oral medication and one with SLT. The necessity of IOP monitoring is strongly emphasized after intravitreal injections of 0.5 mg/0.05 ml ranibizumab.

Evolution of an Astrocytic Hamartoma of the Optic Nerve Head in a Patient with Retinitis Pigmentosa - Photographic Documentation over 2 Years of Follow-Up.

AIM: To report photographically the evolution of an astrocytic hamartoma of the left optic nerve head over a 2-year follow-up in a patient with retinitis pigmentosa. METHODS: A 14-year-old boy was seen in the medical retina clinic with a 3-year history of night blindness. Best corrected visual acuity was 6/18 in both eyes. Colour vision was normal in both eyes and confrontation fields showed peripheral constriction. Fundus examination revealed bone spicule pigmentary changes at the retinal mid periphery typical of retinitis pigmentosa and superficial globules at the margins of both optic nerve heads. Electrodiagnostic tests confirmed moderately severe rod cone dystrophy with macular involvement bilaterally. RESULTS: Two years later, the ocular examination was unchanged except for the appearance of the optic nerve head lesion in the left eye. There was an increase in the size of the lesion which was diagnosed as an astrocytic hamartoma. Further investigations were recommended to exclude neurofibromatosis and tuberous sclerosis. CONCLUSION: Astrocytic hamartomas of the optic nerve head and optic nerve head drusen have both been described in patients with retinitis pigmentosa. They can be a diagnostic dilemma although drusen are more common (10%). To differentiate these two entities it is very important to document any growth during the follow-up period which is suggestive of astrocytic hamartoma rather than optic disc drusen.

Intravitreal bevacizumab for macular edema due to proton beam radiotherapy: Favorable results shown after eighteen months follow-up.

PURPOSE: To evaluate the safety and efficacy of intravitreal injections of bevacizumab (Avastin((R))) as a treatment option for radiation maculopathy secondary to proton beam radiotherapy for choroidal melanoma. CASE: A 61-year-old woman presented with a gradual decrease in left eye visual acuity (VA) 29 months after proton beam radiotherapy for choroidal melanoma. On presentation, her best-corrected VA (BCVA) was 2/10 in the left eye and the intraocular pressure was 15 mmHg. Fundoscopy revealed cystoid macular edema, intraretinal hemorrhages, epiretinal membrane in the posterior pole, and residual tumor scar with exudative retinal detachment and hard exudates in the periphery of the superotemporal quadrant. A treatment with intravitreal injections of bevacizumab (Avastin((R))) was recommended. The injections were performed on a six-weekly basis. RESULTS: The central retinal thickness prior to the treatment was 458 mum. After the first intravitreal injection of bevacizumab, the retinal thickness at the centre of the fovea was reduced to 322 mum. After the third injection, the central retinal thickness was 359 mum and 18 months after presentation, it reduced to 334 mum. The BCVA increased to 3/10 after the intravitreal injections of bevacizumab and remained stable during the follow-up period. The intraocular pressure was within normal range during the follow-up period. CONCLUSION: Bevacizumab should be regarded as a treatment option for macular edema due to proton beam radiotherapy for choroidal melanoma. By reducing the central retinal thickness, intravitreal bevacizumab can improve VA or ameliorate further decline caused by radiation maculopathy.

Complete resolution of a giant pigment epithelial detachment secondary to exudative age-related macular degeneration after a single intravitreal ranibizumab (lucentis) injection: results documented by optical coherence tomography.

AIM: To describe a patient with a giant pigment epithelial detachment (PED) secondary to exudative age-related macular degeneration (ARMD) successfully treated with a single intravitreal ranibizumab (Lucentis) injection (0.5 mg/0.05 ml). METHODS: An 89-year-old woman presented with a six-day history of reduced vision and distortion in the left eye. Best-corrected visual acuity in that eye was 6/15. Fundoscopy revealed a giant PED and exudates temporally to the fovea. Optical coherence tomography showed a PED associated with subretinal and intraretinal fluid. Fluorescein angiography confirmed the diagnosis of an occult choroidal neovascularization. Treatment with intravitreal injections of ranibizumab (Lucentis) was recommended, although the increased risk of retinal pigment epithelium (RPE) rip was mentioned. RESULTS: Four weeks after the first intravitreal Lucentis injection, the visual acuity in the left eye improved to 6/7.5, with a significant improvement of the distortion and a complete anatomical resolution of the PED confirmed by optical coherence tomography. CONCLUSION: Giant PED secondary to exudative ARMD can be successfully treated with intravitreal ranibizumab, despite the increased risk of RPE rip. To our knowledge, this is the first case presenting with complete resolution of PED after a single ranibizumab injection.

Intraocular triamcinolone acetonide for pseudophakic cystoid macular edema: optical coherence tomography and multifocal electroretinography study.

PURPOSE: To evaluate pseudophakic cystoid macular edema (CME) by optical coherence tomography (OCT) and multifocal electroretinography (mf-ERG) and determine the efficacy of intravitreal triamcinolone acetonide injections. METHODS: In this nonrandomized retrospective study, 14 eyes of 14 patients with persistent pseudophakic CME were treated with triamcinolone acetonide injection and were followed up for 1 year. All patients underwent complete ophthalmologic examination including determination of best-corrected visual acuity, slit-lamp examination, tonometry, and funduscopy. Results of OCT and mf-ERG were also recorded before and after the injection. RESULTS: Visual acuity and mf-ERG values increased in all patients after intravitreal triamcinolone acetonide injections. OCT showed improvement of the retinal thickness in the macular area. Temporary increase of intraocular pressure was controlled with topical use of antiglaucoma drops. CONCLUSION: Intravitreal triamcinolone acetonide injection is a promising therapeutic tool for chronic pseudophakic edema resistant to other medical treatment. However, further study is needed to assess the treatment's long-term efficacy, its safety, and the need for retreatment.

Intravitreal use of bevacizumab (Avastin) for choroidal neovascularization due to ARMD: a preliminary multifocal-ERG and OCT study. Multifocal-ERG after use of bevacizumab in ARMD.

PURPOSE: To evaluate by MFERG and OCT the macular function before and after intravitreal use of bevacizumab (Avastin) in eyes suffering from CNV due to ARMD. METHODS: Eighteen eyes with subfoveal CNV due to ARMD were studied before and after intravitreal use of bevacizumab with MFERG and OCT. The post treatment follow up was three months. RESULTS: Before treatment, OCT shows an increase of the retinal thickening of the fovea and the electrical response densities in the fovea and parafovea were decreased in all patients. Three months after treatment, OCT showed a real resolution of the subretinal fluid. The electrical responses in the fovea and parafovea remained the same or slightly improved in some cases. The intraocular pressure remained normal and no inflammation was observed. CONCLUSION: The intravitreal use of bevacizumab may provide anatomical correlates that support the concept of disease amelioration but the functional improvement of the macula three months after treatment is not obvious. However the method is promising and needs further evaluation.

Intraocular triamcinolone acetonide for macular edema due to CRVO. A multifocal-ERG and OCT study.

PURPOSE: To investigate the effectiveness of intravitreal triamcinolone acetonide in the treatment of cystoid macular edema due to central retinal vein occlusion (CRVO). A noncomparative, prospective, interventional case series. METHODS: In this study 15 eyes of 15 patients (9 males and 6 females) with macular edema due to non-ischemic CRVO were treated with intravitreal injection of 4 mg triamcinolone acetonide and followed-up for 1 year. Examination included measurement of best-corrected visual acuity (BCVA) for distance, measurement of intraocular pressure (IOP), fluorescein angiography, foveal retinal thickness measurement by optical coherence tomography (OCT), and multifocal electroretinography recordings (MFERG) preoperatively 3, 6 and 12 months postoperatively. RESULTS: The visual acuity increased to a significant degree at 3 months, to a smaller degree at 6 months but at 12 months there was no significant improvement. The OCT macula thickness improved to a significant level all the follow-up period but with less significance at 12 months. The MFERG recordings from the fovea showed significant improvement at 3 and 6 months. The MFERG from the parafovea area showed significant improvement at 3 and 6 and to a smaller degree at 12 months. The intraocular pressure increased at 3 and 6 months but returned to pretreatment level at 12 months. CONCLUSION: Intravitreal injection of triamcinolone acetonide leads to a significant improvement of mean VA in patients with macular edema due to CRVO. However, this significant effect is not permanent and persists for a maximum of 3-6 months. Thereafter all the indexes tend to deteriorate.