Quantitative assessment of photoreceptor layer in eyes with resolved edema after pars plana vitrectomy with internal limiting membrane removal for diabetic macular edema.

BACKGROUND/AIMS: To evaluate the correlation between visual acuity (VA) and photoreceptor integrity in eyes with resolved diabetic macular edema (DME) after pars plana vitrectomy (PPV). METHODS: Eleven eyes with resolved macular edema following PPV with internal limiting membrane removal for DME were included in this retrospective study. The integrity of the external limiting membrane (ELM) and inner and outer segments (IS/OS) of the photoreceptor junction was evaluated by spectral domain optical coherence tomography. The main outcome measures were percentage of disrupted ELM and IS/OS lines, and correlation between VA and photoreceptor integrity. RESULTS: The mean time after PPV was 78 ± 17 months. The mean lengths of the disrupted ELM and IS/OS lines were 223 ± 167 µm (63%) and 189 ± 175 µm (54%) in the foveola, and 900 ± 522 µm (60%) and 835 ± 582 µm (55%) in the fovea, respectively. Intact ELM and IS/OS lines were positively correlated with VA in both the fovea (p = 0.09 and p = 0.02, respectively) and foveola (p = 0.004 and p = 0.03, respectively). Linear regression analysis showed a statistically significant association of intact ELM and IS/OS lines with VA in the fovea. Disrupted ELM and IS/OS lines had a strong correlation with each other in both the fovea (r = -0.71, p = 0.013) and foveola (r = 0.81, p = 0.02). CONCLUSIONS: The integrity of the ELM and IS/OS lines was positively correlated with VA in eyes with resolved DME after PPV.

Skewed X inactivation in an X linked nystagmus family resulted from a novel, p.R229G, missense mutation in the FRMD7 gene.

AIMS: This study aimed to identify the underlying genetic defect of a large Turkish X linked nystagmus (NYS) family. METHODS: Both Xp11 and Xq26 loci were tested by linkage analysis. The 12 exons and intron-exon junctions of the FRMD7 gene were screened by direct sequencing. X chromosome inactivation analysis was performed by enzymatic predigestion of DNA with a methylation-sensitive enzyme, followed by PCR of the polymorphic CAG repeat of the androgen receptor gene. RESULTS: The family contained 162 individuals, among whom 28 had NYS. Linkage analysis confirmed the Xq26 locus. A novel missense c.686C>G mutation, which causes the substitution of a conserved arginine at amino acid position 229 by glycine (p.R229G) in exon 8 of the FRMD7 gene, was observed. This change was not documented in 120 control individuals. The clinical findings in a female who was homozygous for the mutation were not different from those of affected heterozygous females. Skewed X inactivation was remarkable in the affected females of the family. CONCLUSIONS: A novel p.R229G mutation in the FRMD7 gene causes the NYS phenotype, and skewed X inactivation influences the manifestation of the disease in X linked NYS females.

The sensitivity and specificity of 0.5% apraclonidine in the diagnosis of oculosympathetic paresis.

AIMS: To evaluate the sensitivity and specificity of 0.5% apraclonidine test in the diagnosis of oculosympathetic paresis (OSP). METHOD: Apraclonidine (0.5%) was administered to 31 eyes, nine with a diagnosis of Horner syndrome (HS), 22 with bilateral OSP caused by diabetes, and to 54 control eyes. All were confirmed with the cocaine test. The effects on pupil diameter and upper eyelid level were observed 1 hour later. RESULTS: Apraclonidine caused a mean dilation of 2.04 mm (range 1--4.5) (p<0.001) in the pupils with OSP and it caused pupillary constriction in the control eyes with a mean change of -0.14 mm (range 0.5 to --1) (p<0.05). It caused reversal of anisocoria in all HS cases. Its effects on both pupil diameters and upper lid levels differed significantly between the groups (p<0.001). The mean elevation in the upper lid was 1.75 mm (range 1--4) in the OSP group (p<0.001) and 0.61 mm (range 0--3) in the control group (p<0.001). CONCLUSION: The effect of the apraclonidine (0.5%) test on the pupil diameter was diagnostic for OSP and had at least the same sensitivity and specificity as the cocaine test for the diagnosis of OSP.

Neurologic features of horizontal gaze palsy and progressive scoliosis with mutations in ROBO3.

OBJECTIVE: To review the neurologic, neuroradiologic, and electrophysiologic features of autosomal recessive horizontal gaze palsy and progressive scoliosis (HGPPS), a syndrome caused by mutation of the ROBO3 gene on chromosome 11 and associated with defective decussation of certain brainstem neuronal systems. METHODS: The authors examined 11 individuals with HGPPS from five genotyped families with HGPPS. Eight individuals had brain MRI, and six had electrophysiologic studies. RESULTS: Horizontal gaze palsy was fully penetrant, present at birth, and total or almost total in all affected individuals. Convergence, ocular alignment, congenital nystagmus, and vertical smooth pursuit defects were variable between individuals. All patients developed progressive scoliosis during early childhood. All appropriately studied patients had hypoplasia of the pons and cerebellar peduncles with both anterior and posterior midline clefts of the pons and medulla and electrophysiologic evidence of ipsilateral corticospinal and dorsal column-medial lemniscus tract innervation. Heterozygotes were unaffected. CONCLUSIONS: The major clinical characteristics of horizontal gaze palsy and progressive scoliosis were congenital horizontal gaze palsy and progressive scoliosis with some variability in both ocular motility and degree of scoliosis. The syndrome also includes a distinctive brainstem malformation and defective crossing of some brainstem neuronal pathways.

Optic neuropathy in primary antiphospholipid syndrome in childhood.

Neurologic symptoms associated with antiphospholipid antibodies in children include thrombotic events, unilateral movement disorders, or migraine. We present a 7-year-old girl with bilateral optic neuropathy, cerebral white-matter lesions, and antiphospholipid IgM that responded to prednisone and tended to relapse when it was stopped. Remission was obtained under maintenance corticosteroid therapy, and the antiphospholipid antibodies disappeared. This case suggests a role for antiphospholipid antibodies in the pathogenesis of optic neuropathy in childhood.

Mitochondrial DNA analysis in the Turkish Leber's hereditary optic neuropathy population.

PURPOSE: To define the prevalence of a panel of mitochondrial DNA (mtDNA) mutations associated with Leber's hereditary optic neuropathy (LHON) in the Turkish LHON population. LHON-associated mtDNA mutations have been found in LHON patients from around the world, but the Turkish LHON population has not been studied. METHODS: Thirty-two Turkish patients were defined clinically as having LHON on the basis of painless, subacute, bilateral optic neuropathy and the exclusion of other causes of subacute optic neuropathy. mtDNA was extracted from blood of the 32 probands and assayed for a panel of primary and secondary LHON-associated mtDNA mutations by polymerase chain reaction (PCR)-based methods. We studied three well-known LHON-associated primary mutations (at nucleotide positions 11778, 3460 and 14484) and one common secondary mutation (at nucleotide 15257) in all 32 probands. In addition to these mutations, 18 of the 32 probands were tested for the Complex IV, COX III gene, LHON associated 9804 and 9438 mutations and secondary LHON mutations at nucleotide positions 3394, 4160, 4216, 4917, 5244, 7444, 7706, 13708, 13730 and 15812. RESULTS: Among the 32 probands tested for four common LHON mutations, 3 carried the 14484 mutation, 1 carried the 11778 mutation, 1 carried the 3460 mutation and 1 carried the 15257 mutation. Among the 18 LHON patients who tested for additional mutations, 1 proband harboured the 9804 mutation and 4 carried the secondary mutations at nucleotide positions 4216, 4917 and 13708. CONCLUSION: The results of mtDNA analysis of the Turkish LHON patients appear to be different from those of previous reports.

Granulomatous hypophysitis and bilateral optic neuropathy.

A 53-year-old woman with symptoms of hypopituitarism and ophthalmoplegia was diagnosed as having idiopathic granulomatous hypophysitis and later developed bilateral optic neuritis. She responded well to steroid treatment. Granulomatous hypophysitis is a rare entity, and this is the first reported case associated with optic neuritis.

Visual recovery patterns in children with Leber's hereditary optic neuropathy.

Three patients with Leber's hereditary optic neuropathy (LHON) showed spontaneous improvement in visual acuities after months of legal blindness. Two male patients with bilateral subacute visual loss were 14 years of age at presentation. The first male patient had a mitochondrial DNA mutation at nucleotide position 11778. The second male patient was found to be negative for the designated primary mutations (11778, 14484, 3460) and two of the secondary mutations (15257, 9804). The third patient was a 20-year-old female who presented with bilateral optic atrophy. She had been diagnosed as LHON and was found positive for the 3460 mutation when she was 15. These patients' pattern of visual recovery by developing small islands of normal vision within a central scotoma is characteristic in such rare cases of LHON.

Isolated inferior rectus palsy as a result of paramedian thalamopeduncular infarction.

The authors present the cases of two patients with isolated inferior rectus muscle paresis presumed to be caused by paramedian thalamopeduncular infarction that involved supranuclear descending pathways, just before the inferior rectus subnucleus in one patient, and just before subnucleus or fascicular fibers in the other patient. Both patients had no other associated neurologic dysfunction. The lesions that cause isolated inferior rectus palsy in these patients are documented by magnetic resonance findings. Although vascular ischemic lesions as the cause of isolated inferior rectus palsy were reported previously, to the authors' knowledge, it has not been demonstrated radiologically.

Isolated sixth nerve palsy from pontine infarct.

Isolated sixth nerve palsy associated with pontine infarct is very rare due to close anatomic organization of the structures. A 62-year-old woman, who complained of diplopia, had a diagnosis of sixth nerve palsy. Ophthalmological examination revealed 30 PD left esotropia in primary position with limited abduction of the left eye. Neurologic examination was normal. MR showed a lacunar infarct in the pons consistent with a fascicular lesion. Cerebral angiography was normal. Pontine infarcts causing fascicular lesions should be kept in mind in isolated sixth nerve palsies.

A bad eye and a sore lip.

A 48-year-old woman developed painful visual loss in the left eye, meningismus, and painful oral ulcers. Magnetic resonance imaging of the brain with gadolinium demonstrated enhancement of the left optic nerve. Lumbar puncture showed a lymphocytic pleocytosis, and a biopsy specimen of one of the oral ulcerations was consistent with Behçet's disease. Epidemiologic factors and diagnostic criteria for Behçet's disease are discussed.

Acute blindness and putaminal necrosis in methanol intoxication.

PURPOSE: To review the neuro-ophthalmological and radiological findings of acute methyl alcohol intoxication. METHOD: 8 acute methyl alcohol intoxication cases were evaluated. RESULTS: All patients were male and their ages varied between 21 and 55. At the initial examination, 6 to 12 days after methanol intake, visual acuity ranged from no light perception to counting fingers at 2 meters with no color perception. Bilateral dense central scotomas were detected in patients whose vision was slightly preserved. Pupillary light reactions were either absent or sluggish. In 4 cases, edema of the optic disk and the peripapillary nerve fiber layer was observed. Three months later, optic atrophy had developed. Five patients underwent magnetic resonance imaging. Bilateral putaminal hyperintense lesions on T2 weighted images were observed in 3 cases. Two patients died and autopsy permission could not be obtained. Follow-up examination 12 months later revealed optic atrophy in the other six cases, with no improvement in vision. CONCLUSION: Methanol intoxication is detrimental to health, possibly resulting in blindness and occasionally death. In association with ocular signs and the other systemic and laboratory features, the ophthalmologist should be alert to the diagnosis of methanol intoxication in which visual loss may be the only symptom.