Agreement between optical coherence tomography and digital stereophotography in vertical cup-to-disc ratio measurement.

BACKGROUND: Given the increasing popularity of optical coherence tomography in the diagnosis of glaucoma, we aimed to assess agreement between StratusOCT and stereophotography in measuring the vertical cup-to-disc ratio (VCDR) and examine whether it can be improved by changing the StratusOCT cup-offset. METHODS: In group 1 (79 eyes), VCDR measurements obtained by StratusOCT (using the default cup-offset of 150 microm above the retinal pigment epithelium) and stereophotography were compared. For each eye, the cup-offset was moved upward or downward until the difference disappeared and an adjusted cup-offset was identified. In group 2 (41 eyes), the stereophotography VCDR was compared to the StratusOCT value obtained by using the mean adjusted cup-offset. StratusOCT was used to classify optic disc cups as shallow or deep. RESULTS: In group 1, StratusOCT overestimated VCDR in optic discs with deep cups and underestimated it in those with shallow cups (p < 0.0001). Mean adjusted cup-offsets were 72.8 +/- 92 microm and 191.6 +/- 70 microm for eyes with deep and shallow cups. The 95% limits of agreement (LOA) ranged from -0.21 to 0.17. In group 2, the adjusted cup-offsets enabled us to eliminate the statistical differences in VCDR measurements and improve the 95% LOA (from -0.13 to 0.14). CONCLUSION: Adjusting the StratusOCT cup-offset according to the cup depth improves agreement between StratusOCT and stereophotography in measuring the VCDR.

Association of optic disc size with development and prognosis of Leber's hereditary optic neuropathy.

PURPOSE: To study the optic nerve head (ONH) morphology of patients with Leber's hereditary optic neuropathy (LHON) in a large family from Brazil carrying the 11778/ND4 mutation and in a case series of unrelated Italian families bearing different mitochondrial DNA (mtDNA) pathogenic mutations. METHODS: Enrolled in the study were 15 LHON-affected patients (LHON-affected) and 45 LHON unaffected mutation carriers (LHON carriers) belonging to the previously reported Brazilian SOA-BR LHON pedigree and 56 LHON-affected and 101 LHON carriers from 45 unrelated LHON Italian pedigrees molecularly defined. The LHON-affected were subgrouped according to the extent of visual recovery. All individuals underwent optic nerve head (ONH) analysis by optical coherence tomography. RESULTS: In the Brazilian sample, the mean optic disc area was significantly larger in LHON carriers than in the control group (P=0.002). In the Italian sample, the mean optic disc area and vertical disc diameter were significantly higher in LHON carriers than in both LHON-affected (respectively, P=0.008 and P<0.001) and control subjects (P<0.001 in both cases). The LHON-affected with visual recovery had a significantly larger vertical disc diameter when compared with those without visual recovery (P=0.03). CONCLUSIONS: The results, revealing that the ONH size is larger in LHON carriers than in LHON-affected, suggest a protective role for this anatomic trait. Such a hypothesis is reinforced by the observation that, among the LHON-affected, larger discs correlated with visual recovery and better visual outcome. The findings may be relevant for prognosis and provide a mechanism for identifying nuclear-modifying genes implicated in the variability of penetrance in LHON.

Retinal nerve fiber layer thickness in nonarteritic anterior ischemic optic neuropathy: OCT characterization of the acute and resolving phases.

BACKGROUND: To evaluate longitudinal changes in retinal nerve fiber layer (RNFL) thickness in patients with nonarteritic anterior ischemic optic neuropathy (NAION) using optical coherence tomography (OCT). METHODS: Prospective, observational case series study. Sixteen eyes from 15 consecutive patients affected with NAION were analyzed. The fellow unaffected eyes served as controls. Patients were divided into three different study groups: (1) patients with visual field (VF) defect confined to the inferior hemifield (five eyes), (2) patients with diffuse VF loss (seven eyes), and (3) patients with central or centrocecal scotoma (four eyes). The main outcome was peripapillary RNFL thickness measurement by Stratus-OCT. RESULTS: In group 1, OCT demonstrated RNFL involvement limited to the temporal , superior and nasal optic disc quadrants, both in acute and athophic stages. Diffuse RNFL damage involving all quadrants around the disc was observed in group 2 patients. Group 3, by contrast, revealed RNFL atrophy limited to the superior and temporal sectors of the disc. CONCLUSIONS: OCT can identify different patterns of RNFL involvement specific to different classic VF defects in eyes with NAION. Our results corroborate previous histologic findings in optic nerves affected with NAION.

Leber's hereditary optic neuropathy with childhood onset.

PURPOSE: To characterize the clinical features of childhood-onset Leber's hereditary optic neuropathy (LHON) as defined by a pathogenic mtDNA mutation and age at onset equal to or less than 10 years of age. METHODS: Fifty-six LHON Italian pedigrees including 180 affected individuals were reviewed, and 14 of 18 patients with childhood LHON were enrolled. LHON was classified as acute bilateral, acute unilateral, slowly progressive, and subclinical, according to disease features. All patients underwent a complete ophthalmic examination and optical coherence tomography (OCT), including retinal nerve fiber layer (RNFL) and optic nerve head analysis (ONH), and were compared with age- and optic disc size-matched control groups. RESULTS: The prevalence of childhood LHON in this case series was 11.5%. Five patients had an acute bilateral course, three an acute unilateral course with subclinical signs in the fellow eye, and six a slowly progressive course. Four of five acute patients with acute bilateral disease experienced visual recovery. Slowly progressive cases presented a better visual acuity and visual field outcome than acute cases. A significant diffuse reduction of RNFL was evident in children with acute LHON compared with the control group, whereas a significant reduction of the temporal quadrant was present in the slowly progressive and subclinical LHON cases. Acute LHON children had a smaller disc area and vertical disc diameter than did the control subjects. CONCLUSIONS: This study systematically characterized for the first time the subgroup of LHON with childhood onset. The peculiar clinical and anatomic features of childhood LHON offer insights for the understanding of LHON's pathophysiology as well as a basis for the differential diagnosis of visual loss in childhood.

Detection and quantification of retinal nerve fiber layer thickness in optic disc edema using stratus OCT.

OBJECTIVE: To investigate the ability of optical coherence tomography (OCT) to assess changes in retinal nerve fiber layer (RNFL) thickness in optic disc edema. METHODS: Prospective observational case series in a private eye clinic (Centro Salus). Twelve consecutive eyes (9 patients) with optic disc edema were analyzed, including 6 patients with anterior ischemic optic neuropathy, 1 patient with multiple sclerosis-associated papillitis, and 2 patients with bilateral papilledema. Peripapillary scans of the RNFL were obtained using Stratus OCT (software version 3.0; Carl Zeiss Meditec, Dublin, Calif). Repeated measurements were performed in 7 patients during a follow-up ranging from 8 to 30 weeks. The main outcome was RNFL thickness measurement. RESULTS: Optical coherence tomography detected and quantified diffuse thickening of the RNFL. Compared with eyes in a control group of 75 healthy subjects, eyes with optic disc edema showed a significant increase in the mean RNFL thickness in all quadrants (temporal, P = .002; superior, P<.001; nasal, P<.001; and inferior, P<.001). In patients who were followed up, progressive thinning was observed as the disease evolved toward optic atrophy or clinical resolution. CONCLUSIONS: Optical coherence tomography can identify and measure RNFL edema. This ability of OCT may help elucidate pathophysiological mechanisms in optic disc edema and provide a valuable aid to clinicians.

Selective lesions of rabbit extraocular muscles injected with the anti-AChR immunotoxin saporin-mAb 73.

PURPOSE: To evaluate the effects on extraocular muscles of a skeletal muscle-specific immunotoxin, saporin-mAb 73, as an alternative to botulinum toxin to induce a permanent correction of oculo-facial dystonias or some forms of ocular motility disorders. METHODS: An immunotoxin was prepared with a monoclonal antibody (mAb 73) against acetylcholine receptors of skeletal muscle, linked to saporin, a type 1 ribosome-inactivating protein (RIP) from Saponaria officinalis. Sixteen New Zealand white rabbits were treated with a single injection of immunotoxin directly into the medial rectus muscle of one eye. Four different dosages of 2, 5, 20, or 50 ng saporin-mAb 73 were used. The rabbits were sacrificed at two, 7 and 14 days post-injection. The medial rectus muscle and the retractor bulbi muscle of both the injected and the fellow eyes were taken and serial sections were examined by light microscopy in a blinded manner. RESULTS: Saporin-mAb 73, even at the dosage of 2 ng, brought about focal damage in the extraocular muscles of rabbits without histological changes in adjacent muscles. The histological examination revealed necrotic/apoptotic lesions restricted to the sites of inoculation and largely infiltrated by macrophages. No evident inflammatory reaction was detected at any time and neutrophils were substantially absent. At 14 days after injection, necrosis/apoptosis was still evident and the sclerotic reaction was minimal. CONCLUSIONS: The immunotoxin saporin-mAb 73 injections into the extraocular muscles of rabbits caused focal damage to the muscles. There was no significant inflammatory reaction and muscle fiber loss was present even at the lower doses. Although the lesions were followed for only 14 days, our results suggest that saporin-mAb 73 has potential to cause safe focal muscle damage but longer-term follow-up are needed to investigate the persistence of muscle weakness.