A Japanese Family With Autosomal Dominant Oculocutaneous Albinism Type 4.

Purpose: We report the clinical characteristics of a Japanese family with autosomal dominant oculocutaneous albinism and a SLC45A2 gene mutation. Methods: A total of 16 members of a Japanese family with general hypopigmentation and foveal hypoplasia underwent detailed clinical examinations. We evaluated the severity of foveal hypoplasia using spectral-domain optical coherence tomography (SD-OCT) and graded it according to the criteria of Thomas et al. DNA was extracted from 17 family members and used for genome-wide single nucleotide polymorphism genotyping and linkage analysis. Mutational search was performed for the SLC45A2 gene responsible for oculocutaneous albinism type 4 (OCA4). Results: All 16 patients exhibited hypopigmentation of their hair and/or iris. They showed foveal hypoplasia, including 3 patients with grade 1 foveal hypoplasia, 7 with grade 2, and 6 with grade 3. No patient had grade 4 foveal hypoplasia. Optical coherence tomography showed macular ganglion cell complex thinning in the temporal area, and a slight reduction of visual field sensitivity in the centrotemporal area. A maximum multipoint parametric logarithm of the odds (LOD) score of approximately 2.00 to 3.56 was obtained on chromosome 5, spanning approximately 7.2 Mb between rs13187570 and rs395967 that included the SLC45A2 gene. All affected members showed a novel heterozygous variant, c.208T>C (p.Y70H), in the SLC45A2 gene, which supported a diagnosis of OCA4. Conclusions: The present study reports a very rare family with autosomal dominant OCA4 whose diagnosis was confirmed by a mutational analysis. Most family members exhibited mild general hypopigmentation and low-grade foveal hypoplasia.

Unusual protrusion of conjunctiva in two neonates with harlequin ichthyosis.

BACKGROUND: We present two patients who developed severe protrusion of the conjunctiva and chemosis secondary to Harlequin ichthyosis (HI). CASE REPORTS: Case 1 was a male infant diagnosed with HI who had parchment-like appearance and conjunctival protrusion with severe chemosis. Case 2 was a female infant on whom HI had been suspected before birth through ultrasonography. She showed thickened skin over the entire body and conjunctival protrusion with severe chemosis. For both cases, a vitamin A derivative was applied and the hyperkeratotic layer was peeled off every day. Great care was taken to sterilize and moisten the ocular surface. The conjunctival protrusion gradually improved and other systemic conditions were successfully treated. HI is a rare condition, but affected infants are surviving longer than previously and hence guidelines for ocular management are now required. CONCLUSIONS: Gentle and patient debridement of the hyperkeratotic skin and moisturizing were important in treating the unusual conjunctival protrusion.

Switching from intravitreal ranibizumab to bevacizumab for age-related macular degeneration.

Purpose. To report our experiences in patients with age-related macular degeneration (AMD) treated initially with intravitreal ranibizumab and then switched to bevacizumab. Methods. We retrospectively reviewed the records of 7 patients (7 eyes) who were treated with monthly injections of intravitreal ranibizumab and then switched to injections of bevacizumab (every 6 weeks) for six months. The best-corrected visual acuity measurements (BCVA) and optical coherence tomography (OCT) were performed at the baseline examination and then at each visit. The Wilcoxon signed-rank test was used for the statistical analysis. Results. Following three monthly ranibizumab treatments, there was no significant difference in the BCVA, while the foveal retinal thickness (FRT) significantly decreased (P < 0.01). Switching from ranibizumab to bevacizumab resulted in maintenance (57.2%) of the BCVA and a further decrease in the FRT (P < 0.01) after 6 months. Conclusions. Switching to intravitreal bevacizumab may be effective in patients who wish to discontinue intravitreal ranibizumab treatment due to the high cost.

Functional and morphological evaluation of purtscher retinopathy.

PURPOSE: To determine the extent of retinal damage in Purtscher retinopathy (PR). METHODS: A longitudinal analysis of the retinal morphology and function was made by optical coherence tomography and electroretinography, respectively, on a patient with unilateral PR. RESULTS: Optical coherence tomography showed a marked thickening of the inner retinal layers in the acute phase and a thinning of the inner retinal layers and alteration of the outer layers in the chronic phase. The site of these changes corresponded with the cotton-wool patches. The results of electroretinography indicated reduced inner layer function in the acute phase and partial recovery in the chronic phase. CONCLUSION: The inner and outer retinal layers are altered morphologically and functionally in eyes with PR. The dynamic evaluation on retinal morphology and function may be useful in understanding the pathophysiology of PR.

Optical coherence tomographic evaluation of the outer retinal architecture in Oguchi disease.

BACKGROUND: To report the changes in the optical coherence tomography (OCT) images of the outer retinal layers after prolonged dark adaptation in a patient with Oguchi disease. CASE: A 75-year-old woman showed the typical golden-yellow fundus reflex of Oguchi disease, and the coloration returned to normal after prolonged dark adaptation. Fourier domain OCT (FD-OCT) was performed on the patient's left eye before and after prolonged dark adaptation. OBSERVATIONS: Before dark adaptation, the FD-OCT images at the fovea had three identifiable reflection bands, namely, the external limiting membrane (ELM), the border between the photoreceptor inner and outer segments (IS/OS line), and the retinal pigment epithelium (RPE)/Bruch band. The paramacular area had only the ELM and RPE/Bruch bands. After 4 h of dark adaptation, the IS/OS line was also detected in the paramacular area. CONCLUSIONS: The absence of the IS/OS line in the extramacular regions in the partly dark adapted condition was most likely due to a defect in the rod photoreceptors of this area. The emergence of the IS/OS line after prolonged dark adaptation suggests that microarchitectural changes occur in the photoreceptors and that the changes may be correlated with the improvement of rod function.

Photopic negative response reflects severity of ocular circulatory damage after central retinal artery occlusion.

PURPOSE: To determine the relationship of the photopic negative response (PhNR) of the photopic electroretinogram (ERG) with the degree of circulatory disturbances in eyes following central retinal artery occlusion (CRAO). METHODS: The circulatory disturbance was graded as mild (group 1) when the arm-to-retina transmission time was <30 s, moderate (group 2) when the time was >30 s and severe (group 3) when concurrent choroidal circulatory damage was found. For statistical analysis, groups 1, 2 and 3 were scored as 1, 2 and 3, respectively. Photopic ERGs were elicited by either short-flash (SF) or long-flash (LF) stimuli. RESULTS: Both the SF and LF PhNR were significantly reduced in groups 2 and 3. The PhNR amplitude was negatively correlated with the severity of the ocular circulatory disturbances (p = 0.0498, rho = -0.507 for SF PhNR; p = 0.0050, rho = -0.750 for LF PhNR). CONCLUSION: The amplitude of the PhNR became more reduced as the severity of the circulatory disturbances increased in eyes with CRAO.

Changes in retinal thickness are correlated with alterations of electroretinogram in eyes with central retinal artery occlusion.

BACKGROUND: We investigated the relationship between the retinal thickness and electroretinogram (ERG) components in patients with central retinal artery occlusion (CRAO). METHODS: The optical coherence tomographic (OCT) images and ERGs of the nine patients (six men and three women; mean age, 61.8 years) were retrospectively analyzed. The thickness of the inner and outer retinal layers at 1 and 2 mm nasal and temporal to the fovea was measured in the horizontally scanned OCT images. The ratio of the inner layer thickness/sensory retinal thickness (IT/ST ratio) was calculated. The amplitudes of the a- and b-waves of the mixed rod-cone ERGs and the photopic negative response (PhNR) of the photopic ERGs were analyzed. The ratio of the amplitude of each component in the affected eye to that of the healthy fellow eye (a/f ratio) was calculated. RESULTS: In the chronic phase (1 to 8 months after onset, eight eyes), the inner layer was significantly thinner than that in the acute phase (P = 0.0147, 0.0076, 0.002, and 0.0003 for 2 mm nasal, 1 mm nasal, 1 mm temporal, and 2 mm temporal respectively, within 5 days of onset, six eyes), while the thickness of outer layer was not significantly changed. The ERGs were recorded 6.4 +/- 1.5 days after the onset of CRAO. The median of the a/f ratio was 0.84 in the a-wave, 0.56 in the b-wave, and 0.27 in the PhNR. The IT/ST in the chronic phase was positively correlated with the a/f ratio of the amplitude of the PhNR. CONCLUSIONS: Measurement of retinal thickness by OCT can be useful for monitoring the changes following CRAO. The correlation between the retinal thickness, especially inner layer thickness, and the ERG components was determined, suggesting that the PhNR in the acute phase might be a good indicator for predicting the thinning of the damaged retina in the chronic phase.

Severe acute ocular ischemia associated with spontaneous internal carotid artery dissection.

A healthy 40-year-old man developed unilateral ocular ischemic syndrome as the only manifestation of a spontaneous internal carotid artery dissection.

Effect of spatial frequency of stimulus on focal macular ERGs in monkeys : fmacERG dependence on the spatial-frequency.

PURPOSE: To determine the effect of the spatial frequency of a small grating stimulus centered on the macula on the focal macular ERGs (fmacERGs) of monkeys. METHODS: fmacERGs were recorded from eight eyes of four adult monkeys (Macaca fuscata). The spatial frequency of the stimulus was changed from 0.25 to 8 cycles/degree. The luminance of the light bars was 10 cd/m(2), and the contrast was 95%. The stimulus was flashed on and off with an on duration of 100 ms and an off duration of 150 ms (4 Hz). The stimulus was centered on the fovea and subtended 12.7 degrees at the cornea. The luminance of the steady light-adapting background was 3.5 cd/m(2). The location of the stimulus on the retina was monitored throughout the recordings. The effects of the spatial frequency of the stimulus on the amplitudes and implicit times of the a-waves, b-waves, and oscillatory potentials (OPs) were determined. fmacERGs were also recorded following intravitreal tetrodotoxin (TTX). RESULTS: The amplitudes of the a- and b-waves did not change with changes in the spatial frequency of the stimulus. The OPs, on the other hand, responded best to the lowest spatial frequency, and the OPs after the first two were attenuated at intermediate and higher frequencies (Wilcoxon signed-rank test: P < 0.05). TTX reduced all OP wavelets in monkeys. CONCLUSIONS: The OPs of the photopic macular ERGs are affected by the spatial frequency of the stimulus and are reduced by TTX, consistent with their being generated by inner retinal neurons.