Leonard M. Parver

Choroidal blood flow as a heat dissipating mechanism in the macula.

We studied the possible role of the choroidal circulation in stabilizing the temperature environment of the retina and the retinal pigment epithelium. Temperature measurements were taken from the retina and choroid of the monkey eye while the ambient illumination and choroidal blood flow were varied. The results showed that the choroidal circulation plays a significant role in dissipating heat generated by the focusing of light at the macula and suggest that this function may be a primary reason for the relatively high values of choroidal blood flow.

Observations on monkey eyes exposed to light from an operating microscope

Two cynomolgous monkeys were exposed to the light of an operating microscope. One eye was exposed to the light with the blue end of the spectrum filtered, while the other was exposed to unfiltered light. Neither group of eyes showed ophthalmoscopic evidence of a discrete retinal lesion. The eyes exposed to unfiltered light, however, showed histologic evidence of foveomacular change. The eyes exposed to filtered light showed lesser changes.

Efficacy and safety of ketotifen fumarate 0.025% in the conjunctival antigen challenge model of ocular allergic conjunctivitis

PURPOSE To determine the duration of action of ketotifen 0.025% eye drops vs placebo taken as single or multiple doses in an allergen challenge model. DESIGN Two randomized, multicenter, double-masked, contralateral placebo-controlled studies, one a single-dose and one a multiple-dose study. METHODS Two conjunctival provocation tests (CPTs) were initially conducted to confirm reproducibility of subject responses in both studies. Subjects in study 1 (n = 87) received single doses of ketotifen in one eye and placebo in the other 15 minutes, 6 hours, and 8 hours before CPT. Subjects in study 2 (n = 85) received ketotifen or placebo once 8 hours before CPT. Single-dose efficacy results were used to further qualify a subject as a responder. Responders were re-randomized to a 4-week twice daily dosing regimen with a CPT 8 hours after the final dose. In both studies, ocular symptoms were assessed at three time points 3 to 15 minutes after challenge. There were no significant differences in adverse events between groups. RESULTS For both studies, ocular itching and vascular injection were significantly reduced (P <.003) at all time points after instillation of ketotifen, with a maximum reduction at 7 minutes postchallenge. In study 2, chemosis, tearing, and lid swelling were also assessed and were significantly reduced (P <.008) after instillation of ketotifen. CONCLUSIONS Ketotifen 0.025% eye drops were safe and statistically effective in preventing ocular itching, injection, and other signs and symptoms of allergic conjunctivitis at 15 minutes, 6 hours, and 8 hours after a single dose and at 8 hours after the final dose of a 4-week twice daily regimen.

The stabilizing effect of the choroidal circulation on the temperature environment of the macula.

A major physiologic function for the high-flow choroidal circulation is the stabilization of the temperature environment of the retina. This is especially important in the macular region, which lies at the focal point of the eyes optical system. Observations of temperature changes in the macula under varying conditions of ambient illumination and choroidal blood flow have established that the choroidal circulation serves a dual purpose in stabilizing retinal tissue temperature, acting both as a heat source and a heat sink, depending on prevailing tissue temperatures.

Evidence for enhanced tissue factor expression in age-related macular degeneration.

Tissue factor (TF) is the primary initiator of blood coagulation. In addition to hemostasis, TF can initiate intracellular signaling and promote inflammation and angiogenesis, the key processes underlying the pathogenesis of age-related macular degeneration (AMD). AMD, the leading cause of irreversible blindness among the elderly, involves many genetic and environmental risk factors, including oxidative stress and inflammation. In this study, TF expression was examined in human AMD tissue and in the eyes of a model of AMD, the Ccl2−/−/Cx3cr1−/− (DKO) mouse, as well as in the ARPE-19 cell line after lipopolysaccharide (LPS) and H2O2 stimulation. Total RNA was extracted from tissue samples and further analyzed by real-time RT-PCR. Immunohistochemistry was performed to evaluate TF protein expression. In the human retina, a 32-fold increase of TF mRNA expression was detected in AMD macular lesions compared with normal maculae. TF protein expression was also enhanced in human AMD maculae. Similarly, TF transcript and protein expression were moderately increased in retinal lesions, neuroretinal tissue, and cultured RPE cells of DKO mice compared with age-matched wild-type mice. TF expression level correlated with age in both wild-type and DKO mice. In order to better understand how AMD might lead to enhanced TF expression, 1, 5, and 10 μg/ml LPS as well as 100 and 200 μM H2O2 were used to stimulate ARPE-19 cells for 24 and 2 h, respectively. LPS treatment consistently increased TF transcript and protein expression. H2O2 alone or in combination with LPS also moderately enhanced TF expression. These results indicate that upregulated TF expression may be associated with AMD, and inflammatory and oxidative stress may contribute to TF expression in AMD eyes.

The Clinical Characteristics of Presumed Choroidal Nevi Observed in Green Light

Thirty-two patients with presumed choroidal nevi were examined and photographed in both white and green light. Twenty-one lesions disappeared or became markedly attenuated when viewed with green light. The remaining 11 lesions did not disappear when viewed with green light. Many of these nevi demonstrated visual field defects and fluorescein angiographic abnormalities. The clinical applications of green light ophthalmoscopy and photography are discussed.

Correlation of full-thickness corneal wound length with endothelial cell loss

We studied 12 patients who had sustained penetrating corneal lacerations with corneal wound lengths ranging from 1 to 9 mm to determine whether wound size was directly proportional to endothelial cell loss 3 or more months after injury. Endothelial cell counts in the uninjured eye averaged 2973 +/- 330 cells/mm2 (range, 2500 to 3700). In the injured eye, near the wound (less than 2 mm from the wound), the cell counts averaged 1260 +/- 590 cells/mm2 (range, 575 to 2500); away from the wound, where cells appeared healthiest, counts averaged 1619 +/- 544 cells/mm2 (range, 850 to 2750). The average total cell loss near the wound was 1713 +/- 622 cells/mm2 (range, 500 to 2575), vs 1354 +/- 582 cells/mm2 (range, 250 to 2150) away from the wound, compared with the uninjured eye. Cell loss near the wound was not significantly different from that away from the wound. There was a positive correlation between wound length and total cell loss measured both near the wound (r = 0.830) and away from the wound (r = 0.755). Pars plana lensectomy was not associated with detectable additional cell loss. Our results suggest that patients with corneal lacerations sustain significant endothelial cell loss, which correlates closely with wound length, and that patients with larger wounds may be at greater risk for developing corneal decompensation with additional procedures or trauma.