Choroidal vascular permeability in visually regulated eye growth.

The choroidal thickness fluctuates both diurnally and in response to changes in visual input. The fluctuations may represent a physiologic means of aligning the retinal photoreceptors with the focal position of distant images during the emmetropization process. To evaluate the basis for choroidal thickness changes, we studied the sources of the extravascular fluid in the chick choroid in two visually-regulated ocular growth conditions: accelerated ocular growth in goggle-induced form-deprivation myopia and ocular growth retardation in the recovery from myopia after goggle removal. Two week old chicks, controls, myopic and those recovering from myopia, received fluorescein dextran (MW = 140,000) as a tracer. It was given by intravenous injection to identify a potential vascular pathway and by intracameral injection to identify a potential pathway from the anterior chamber to the suprachoroidal space. Using a microscopically positioned needle, clear fluid was aspirated from the suprachoroidal space of the enucleated chick eye; this fluid presumably corresponds to the contents of the lacunae, prominent lymphatic-like structures of the chick choroid. Plasma, aqueous humor and suprachoroidal fluid were sampled 1 hr after injection and assayed for both protein content and the tracer dye. Sulfated glycosaminoglycans were assayed in the suprachoroidal fluid, choroid and sclera under each experimental condition. In control chicks, aqueous humor and suprachoroidal fluid protein concentrations were about 0.8 and 9% of plasma levels respectively. Aqueous humor protein concentration was unaltered in myopic or recovering eyes. Suprachoroidal fluid protein concentration in myopic eyes fell dramatically to 1.5% of plasma levels (P < 0.001). In contrast, recovery from myopia led to a marked increase in suprachoroidal fluid protein level to 30% of that in plasma (P < 0.001). None of the procedures affected suprachoroidal fluid protein in the contralateral control eyes. In all three groups of chicks, fluorescein dextran distribution in the suprachoroidal fluid at 1 hr after intravenous injection tracked protein levels, with reduced levels in myopic eyes and elevated levels in recovering eyes. After intracameral injection, suprachoroidal fluid dextran levels were higher in injected eyes of control chicks (P < 0.01) and in recovering eyes (P < 0.001) but lower in myopic eyes (P < 0.01), compared to the levels in the respective contralateral non-injected eyes in each group. Sulfated glycosaminoglycan levels were at the limits of detection in the suprachoroidal fluid under all conditions and, on a whole choroid basis, were unaltered in the choroid in either myopia or recovery. Suprachoroidal fluid is lymph-like in nature and largely derives from plasma. Sulfated glycosaminoglycan levels do not seem to regulate the fluid content of the choroid in either myopia or recovery. Instead, the changes in protein and marker dye levels in myopic and recovering eyes suggest markedly altered choroidal circulatory dynamics and capillary permeability in both conditions.

Discordant retinoblastoma in monozygotic twins.

PURPOSE: We report cases of discordant retinoblastoma in twins confirmed to be monozygotic by DNA analysis. METHODS: Twin A demonstrated severe, bilateral, multifocal retinoblastoma, which was recalcitrant to external beam irradiation and chemoreduction. Twin B has not demonstrated retinoblastoma. DNA analysis was performed with polymorphic microsatellite markers to confirm monozygosity. Single-stranded conformation polymorphism and Southern blot analysis of the retinoblastoma gene were performed. RESULTS: Molecular genetic analyses confirmed monozygosity but failed to disclose a retinoblastoma gene mutation in either twin. CONCLUSIONS: The extreme phenotypic discordance may best be explained by an unidentified, postzygotic retinoblastoma gene mutation in early embryonic development of the affected twin.

Autonomic denervations influence ocular dimensions and intraocular pressure in chicks.

Choroidal thickness and axial eye length in the chick undergo day/night fluctuations that can also be modulated by visual experience. In the present study, we tested the effect of parasympathetic and sympathetic denervations on both day/night and image dependent changes in ocular dimensions. We also correlated such changes with fluctuations in intraocular pressure. Parasympathectomy influenced choroidal thickness and its day/night fluctuation, but had no effect on vision dependent choroidal thickness modulation. Parasympathectomy also influenced-to a lesser extent-axial length and reduced the axial growth response to form vision deprivation. Sympathectomy had little effect on ocular dimensions, but reduced the day/night differences in intraocular pressure. We conclude that (a) the parasympathetic nervous system influences both choroidal thickness and axial length and participates in the neural control mechanism leading to form deprivation myopia and, (b) the day/night fluctuations of choroidal thickness and axial length are unlikely to be explained by fluctuations in intraocular pressure. For the regulation of choroidal thickness, we hypothesize the existence of two independent mechanisms. One involves the parasympathetic nervous system; it influences the day/night choroidal thickness fluctuation. The other uses a separate pathway and is driven by visual input.

Relation of optical coherence tomography to microanatomy in normal and rd chickens.

PURPOSE: To elucidate the relation between optical coherence tomography (OCT) scans and retinal histology in normal and retinal degeneration (rd) chickens. METHODS: Retinas from adult normal and rd chickens were examined in vivo with OCT at 850 nm and compared quantitatively with stained cryosections of unfixed retinas from the same locations. RESULTS: The nerve fiber layer (NFL) and inner plexiform layer (IPL) show homogeneous backscatter throughout their thicknesses. NFL reflectivity is approximately 0.6 log units higher than that of the IPL. The inner nuclear layer shows a low reflectivity; the properties of reflections from ganglion cell and outer nuclear layers are indeterminate. The outer retina and choroid form a large reflective complex. Photoreceptor inner segments produce the highest of these reflections in normal chicken retinas, approximately 1.5 log units higher than that of the IPL. The retinal pigment epithelium also has a relatively large backscatter coefficient and is the dominant reflector in rd retinas that lack photoreceptors. Choroidal pigment produces an intermediate level of backscatter and is the largest attenuator of signal at 850 nm. CONCLUSIONS: Quantified OCT signals have a predictable relationship to histology and pathology in chicken retinas. The results from rd retinas represent a first step toward in vivo quantitation of retinal structure in retinal degenerative disease.

Induction of axial eye elongation and myopic refractive shift in one-year-old chickens.

Depriving the eyes of neonatal animals of form vision induces axial eye elongation and ipsilateral myopia. We studied one-year-old chickens, an age at which full body growth has been attained, to learn if form deprivation myopia can develop at a later stage. We found that ocular reactivity to visual form deprivation continues in one-year-old chickens; but both the growth stimulation and the myopic shift in refraction are attenuated compared with newly hatched birds. Neurochemical changes in visually deprived eyes of one-year-old chickens parallel those in newly hatched chicks: ipsilateral decreases in retinal dopamine and in the activity of ciliary ganglion and uveal choline acetyltransferase. These findings strengthen the relevance of the form deprivation model to more common human myopia and suggest a common eye growth control mechanism at both ages.

Ocular axial length and choroidal thickness in newly hatched chicks and one-year-old chickens fluctuate in a diurnal pattern that is influenced by visual experience and intraocular pressure changes.

Low coherence laser Doppler interferometry (LDI) allows high precision measurements of the axial length of the eye and of the thickness of the individual layers of the ocular fundus. Here, we used LDI to monitor diurnal changes in these dimensions in eyes of newly hatched chicks and one-year-old chickens with normal or altered visual input. In chicks and chickens with normal visual experience, axial eye length displays diurnal fluctuations increasing during the light phase. Choroidal thickness also exhibits a diurnal pattern, shrinking during the day and expanding during the night. Retinal thickness does not vary. Based on the pressure compliance of the enucleated chick eye, the diurnal intraocular pressure (IOP) fluctuation could contribute both to the increase in axial length and to daytime choroidal shrinkage. Following deprivation of form vision by unilateral goggle wear, occluded chick eyes demonstrate enhanced axial elongation. Diurnal fluctuations in axial length but not in choroidal thickness are temporarily disrupted. The retina of form deprived eyes thins approximately 10% in five days. In contralateral eyes, the diurnal patterns of both axial length and choroidal thickness fluctuations are also disrupted. Following occluder removal in chicks, choroidal thickness increases for several days during both the light and dark phase, leading to its overall expansion. Retinal thickness returns to baseline. When deprived of form vision for five days, the eyes of year-old chickens do not exhibit measurable axial elongation. Diurnal patterns of fluctuation in axial length and choroidal thickness are however disrupted. After goggle removal, axial length fluctuation is restored to normal, but the diurnal choroidal thickness pattern is inverted. In contralateral eyes, choroidal thickness exhibits normal diurnal fluctuations both during and after form vision deprivation. In conclusion, axial length and choroidal thickness fluctuations are influenced by visual experience in both newborn chicks and one-year-old chickens. In selected instances a binocular interaction regarding axial length and choroidal thickness changes is suggested, the effect weakening with age.

Validation of laser Doppler interferometric measurements in vivo of axial eye length and thickness of fundus layers in chicks.

Purpose. Laser Doppler interferometry (LDI) permits the measurement of intraocular distances to a precision of better than 20 microm. The signal complex from the posterior segment of the eye consists of four peaks in the chick, an animal frequently used in ocular development studies. The present study sought to identify anatomical landmarks corresponding to these LDI peaks. Methods. Distances obtained with LDI at the posterior pole were compared to axial length components measured with three independent methods: vernier calipers, tissue sections and high frequency A-scan ultrasound. Results. LDI reflections appear to originate from the retinal inner limiting membrane, Bruch's membrane and the inner and outer scleral surfaces. Conclusions. The non-invasive and highly precise nature of LDI measurements enables repetitive and accurate assessment of intraocular distances. Such measurements should prove particularly useful for the assessment of short-term cyclic variations in intraocular distances as well as post-natal eye growth.