RECURRENCE RATE OF CYSTOID MACULAR EDEMA WITH TOPICAL DORZOLAMIDE TREATMENT AND ITS RISK FACTORS IN RETINITIS PIGMENTOSA.

PURPOSE: To investigate the rate of the recurrence of cystoid macular edema (CME) secondary to retinitis pigmentosa (RP) after the initiation of topical dorzolamide and the recurrence risk factors. METHODS: We retrospectively analyzed the data of RP patients at Kyushu University Hospital. We included patients who showed a treatment response to 1.0% topical dorzolamide. The day of treatment initiation was set as the baseline. Topical dorzolamide treatment was continued during the follow-up. The recurrence of CME (defined as a >20% increase in central subfield thickness compared to previous visit, or a central subfield thickness value that exceed baseline value) was evaluated at each follow-up visit. Risk factors for RP-CME recurrence were analyzed by Cox proportional hazards modeling. A Kaplan-Meier survival analysis was used to evaluate the time to recurrent RP-CME. RESULTS: Forty RP-CME patients showed a treatment response to topical dorzolamide. During the mean 3.9-year follow-up, 14 patients exhibited recurrence; its rate was 15.6%, 34.7%, and 48.7% at 1, 3, and 5 years, respectively. A high baseline central subfield thickness was significantly associated with recurrent (hazard ratio 1.11, 95% CI: 1.05-1.18, P = 0.0004). CONCLUSION: The recurrence rate of RP-CME increased with time. A high baseline central subfield thickness value was a risk factor for recurrence.

Demonstration of anatomical development of the human macula within the first 5 years of life using handheld OCT.

PURPOSE: To demonstrate the anatomical development of the human macula using handheld spectral domain optical coherence tomography (SD-OCT) during the first 5 years of life. METHODS: This study is a cross-sectional, observational case series. Thirty-five normal eyes of 35 full-term/late preterm infants and children under 5 years of age were included. Handheld SD-OCT was used to image the macula of each eye. The data were analyzed using the Duke OCT Retinal Analysis Program v17 software. Retinal thickness maps were generated for the total retinal thickness (TRT), the inner retinal layers thickness (IRL), and the photoreceptor layer thickness (PRL). Based on the early treatment diabetic retinopathy study macular map, average thickness measurements were taken at 4 circles centered on the fovea (diameter): the foveal center (0.5 mm), sector 1 (S1) (1 mm), sector 2 (S2) (3 mm), sector 3 (S3) (6 mm). RESULTS: The median age at participation was 24 months (range 5-52 months). The TRT increased throughout the first 5 years of life, and this increase was statistically significant at the foveal center and S1 (p = 0.01, p = 0.016, respectively). The IRL did not show any significant change in thickness from birth and throughout the first 5 years of life. The PRL thickness showed thickening in the first 24 months of age at the foveal center and S1 which was statistically significant at S1 (p = 0.066, p = 0.016, respectively). Interestingly, this PRL thickness increase plateaus beyond 24 months of age. The photoreceptors inner segment/outer segment (IS/OS) band was identified as a distinct layer in all our subjects. CONCLUSION: Our findings conform with the literature that the anatomical development of the macular IRL completes before 5 months of age and hence before the PRL. We also identify 24 months of age as an important developmental milestone for photoreceptors development in the human macula.

There's something in the air.

A 20-year-old woman presented with bilateral constant positive visual phenomenon since she was 9 years old. The symptoms had been worsening and becoming more intrusive in the last 3 years. Recently she has also had a migrainous episode. All ophthalmic and neurological investigations were normal. Her symptoms met the diagnostic criteria for visual snow. The diagnosis was explained, and the patient was reassured. Ophthalmologists and neurologists need to be aware of this condition to avoid over investigation and worsening of patient anxiety.

Juvenile Macular Degenerations.

In this article, we review the following 3 common juvenile macular degenerations: Stargardt disease, X-linked retinoschisis, and Best vitelliform macular dystrophy. These are inherited disorders that typically present during childhood, when vision is still developing. They are sufficiently common that they should be included in the differential diagnosis of visual loss in pediatric patients. Diagnosis is secured by a combination of clinical findings, optical coherence tomography imaging, and genetic testing. Early diagnosis promotes optimal management. Although there is currently no definitive cure for these conditions, therapeutic modalities under investigation include pharmacologic treatment, gene therapy, and stem cell transplantation.

A role for the macular carotenoids in visual motor response.

OBJECTIVES: Lutein (L), zeaxanthin (Z), and meso-zeaxanthin are the dominant carotenoids within the central retina (there, termed macular pigment, MP). L is also the dominant carotenoid in the brain. The presence of L and Z in both motor and visual areas of the central nervous system is consistent with a role of these carotenoids in visual-motor behavior. The purpose of this study was to provide a first test of this hypothesis. METHODS: Balance ability (measured via the Standing Leg Test) and simple reaction time (measured via a stimulus appearing in one of four quadrants of a computer monitor) were measured in 49 subjects (mean age = 54.8 years). Fixed and variable reaction time, and coincidence anticipation ability (estimating the arrival of the stimulus at a target location moving at four velocities) were assessed in 106 younger subjects (mean age = 23 years) using a customized device. MP optical density was measured in all subjects via customized heterochromatic flicker photometry. RESULTS: MP optical density was significantly (P < 0.05) related to reaction time and to balance ability for the older subjects. Even for the younger group, MP optical density was significantly (P < 0.05) related to fixed and variable position reaction time, as well as coincidence anticipation errors, at high speed. DISCUSSION: L and Z status has been linked to benefits in cognitive function in past research. The present results, and the selective presence of L and Z in visual and motor areas in the brain, are consistent with these carotenoids having a role in visual and motor integration.

[Carotenoids of the human eye in prenatal and early postnatal development].

The review deals with the role of carotenoids in the formation of the structural and functional differentiation of the macula--the area of the highest visual acuity of the human retina. The review also presents the data on detection of carotenoids (lutein) in the vitreous body of the human eye during its prenatal development and discusses their possible role in the development of the retina, particularly in relation to differentiation of the macular area. Macular dystrophy has been considered till recently as senile pathology. According to modern ophthalmologic observations, the number of cases of appearance of this pathology increases in young humans. Such a shift can be prevented by addition of carotenoids to the diet. This permits a conclusion that the permanent presence of carotenoids in the course of the whole human life is necessary for the formation and retention of structural and functional integrity of the macula.

Developmental macular disorders: phenotypes and underlying molecular genetic basis.

The developmental macular disorders form part of a heterogeneous group of retinal conditions that are an important cause of visual impairment in children. The macular abnormality is present from birth and is usually non-progressive but visual loss may occur as a result of complications such as choroidal neovascularisation. To date, most of the causative genes have not been identified but with the advent of next generation sequencing, it is likely that the genetic basis of these disorders will soon be elucidated. Improved knowledge of the underlying molecular genetics and disease mechanisms will raise the possibility of future treatments for these disorders, for which there are no specific therapies available at the present time.

Anatomy and development of the macula: specialisation and the vulnerability to macular degeneration.

The central retina in primates is adapted for high acuity vision. The most significant adaptations to neural retina in this respect are: 1. The very high density of cone photoreceptors on the visual axis; 2. The dominance of Midget pathways arising from these cones and 3. The diminishment of retinal blood supply in the macula, and its absence on the visual axis. Restricted blood supply to the part of the retina that has the highest density of neural elements is paradoxical. Inhibition of vascular growth and proliferation is evident during foetal life and results in metabolic stress in ganglion cells and Muller cells, which is resolved during formation of the foveal depression. In this review we argue that at the macula stressed retinal neurons adapt during development to a limited blood supply from the choriocapillaris, which supplies little in excess of metabolic demand of the neural retina under normal conditions. We argue also that while adaptation of the choriocapillaris underlying the foveal region may initially augment the local supply of oxygen and nutrients by diffusion, in the long term these adaptations make the region more vulnerable to age-related changes, including the accumulation of insoluble material in Bruch's membrane and beneath the retinal pigment epithelium. These changes eventually impact on delivery of oxygen and nutrients to the RPE and outer neural retina because of reduced flow in the choriocapillaris and the increasing barriers to effective diffusion. Both the inflammatory response and the sequelae of oxidative stress are predictable outcomes in this scenario.

Changes in macular function throughout adulthood.

Recent reports suggest that the neural system is the principal cause of loss of visual function with age and that senile lenticular and pupillary changes are of minor importance. In order to investigate this neural deterioration further we measured Logmar visual acuity and photostress recovery time (PSRT) in 61 subjects over an age range of 19 to 78 years. The magnitude of the PSRT reflects the efficiency with which the visual system recovers from exposure to a glare source and is principally dependent upon the integrity of the photoreceptors and the retinal pigment epithelium. The results indicate that macular function declines significantly throughout adulthood.

A qualitative and quantitative analysis of the human fovea during development.

The anatomical development of the human fovea has been sampled from 22 weeks gestation to adulthood, using both qualitative and quantitative methods. The foveal depression continues to deepen after birth until 15 months, due to the migration of the cells of the inner retina toward the periphery. Before birth the rod-free zone or foveola is over 1000 microns in diameter, but it becomes progressively narrower after birth because of a centralward migration of cones. It reaches the adult diameter of 650-700 microns by 45 months of age. Postnatally, foveolar cone development is characterized by maturation, elongation, and an increase in packing density. Foveolar cone diameter changes markedly after birth, going from 7.5 microns at 5 days postnatal to 2 microns by 45 months. During this time the foveolar cone develops both its outer segment and basal axon process (fiber of Henle). This combination of elongation and centralward migration results in an increase of foveolar cone density from 18 cones/100 microns at 1 week postnatal to 42 cones/100 microns in the adult. Measures of foveola width and cone diameter reach the adult stage of development at 45 months of age, but the two important visual factors of outer segment length and cone packing density still are only half the adult values at 45 months of age.

Macular development in the premature infant.

To classify the ophthalmoscopic appearance of the developing macula, I performed retinal examinations on 129 premature neonates. In normal infants, the classification ranged from 34 weeks of gestational age when pigment was first evident in the macula, through the development of the annular ring reflex of the macula and foveolar reflex, to a mature (adult-appearing) macula at 42 weeks. This sequence allowed the observer to estimate the gestational age of the older premature neonate from the appearance of the macular area. Babies who had, or subsequently developed, retinopathy of prematurity showed a statistically significant two-week delay in macular development in the later stages. This may be the first evidence of a direct macular insult in retinopathy of prematurity.

The morphological development of the human fovea.

The development of the human fovea has been traced from 22 weeks gestation to 45 months postpartum using aldehyde-fixed, plastic embedded, serially-sectioned normal retinas. Five anatomical indicators of foveal maturity were used in this study: the shape of the foveal curvatures; the presence of the transient layer of Chievitz; the width of rod-free zone in the central retina; the width and length of the individual foveal cones; and the number and thickness of layers of nuclei within the fovea. The future fovea is identifiable at 22 weeks by the presence of a thick layer of ganglion cells and a photoreceptor layer containing only cones. By 1 week after birth, there is a shallow foveal depression, but the thick cones still lack outer segments and are only 1 cell deep in the fovea. The inner nuclear layer contains a thick transient layer of Chievitz. As judged by these anatomical criteria and compared to normal adult foveas similarly processed, the human fovea reaches maturity between 15 and 45 months of age.