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| October 2001 | Inside IOVS | Volume 42/11 |
| Steps Towards Treatments for Ocular Diseases |
Botulinum and Esotropia
Children may develop a constant esotropia after 6 months of age which is not correctable, or only partially, by spectacle prescription. Surgery or botulinum toxin injection have been indicated to treat them, but the benefit of the latter is controversial and factors influencing its efficacy unknown. After prospectively following 68 children treated with botulinum toxin, Tejedor and Rodríguez (p. 2542) conclude that this treatment is effective long-term, and the best candidates for it are children with minimal amblyopia, high hypermetropia and small angle esotropia. If properly selected, children might avoid surgery and have their misalignment corrected by a single botulinum injection.
PGs and Scleral Permeability
Recent investigations have demonstrated that intravitreal injections of some macromolecules have the potential for treating several diseases of the ocular posterior segment. However, repeated intravitreal injections are not practical for clinical treatment, and transcorneal penetration following topical treatment is limited for macromolecules larger than 10 kDa. Aihara et al. (p. 2554) demonstrate that exposure of human sclera organ cultures to latanoprost, a widely used IOP-lowering prostaglandin analogue, enhances transscleral permeability of fibroblast growth factor-2, a 16-kDa peptide growth factor known to promote the survival of retinal neurons. This raises the possibility that transscleral delivery of peptide therapeutics to posterior segment tissues can be enhanced by topical treatment with latanoprost.
ICAM-1 and LFA-1 in Uveitis
Migration of leukocytes from the blood stream to perivascular tissue involves a sequence of steps, each of which is a potential target for anti-inflammatory therapy. Becker et al. (p. 2563) have used intravital microscopy to show that antibodies to intercellular adhesion molecule (ICAM)-1 and leukocyte functional antigen (LFA)-1 block leukocyte sticking and infiltration, but not the initial rolling step in endotoxin-induced uveitis. One may therefore predict that combination therapy involving an agent that blocks ICAM-1 and LFA-1 would be most effective if the second agent inhibited a different step, such as rolling.
V-Z Virus and Arteritis
Giant cell arteritis (GCA) is a chronic arterial inflammation with ocular involvement. The etiology is unknown, but the histological characteristics are consistent with an infectious disease. Mitchell and Font (p. 2572) investigated the potential association of varicella-zoster virus (VZV) with GCA by molecularly evaluating temporal artery biopsy specimens. The authors detected VZV DNA in about one-fourth of the GCA-positive specimens, but not in the GCA-negative specimens. These findings provide some of the first direct evidence that VZV might be an etiological agent for GCA and could be important in the management of this disease.
Ca2+ Antagonists and CAR
It was recently found that recoverin acts as an autoantigen recognized by sera from patients with cancer-associated retinopathy (CAR), and that CAR-like retinal dysfunction was produced by intravitreous administration of anti-recoverin antibody in Lewis rat eyes. In the present study, Ohguro et al. (p. 2589) found beneficial effects of nilvadipine, a Ca2+ antagonist, and dark adaptation on the retinal degenerations using these models. The present data will facilitate clinical application of systemic administration of a Ca2+ antagonist to CAR in human.
COX-2 and POAG
Despite the obvious effects of prostaglandins (PGs) in the eye, the ocular distribution of the producing enzymes is not known. Maihöfner et al. (p. 2616) demonstrate that both PG-producing enzymes, cyclooxygenase (COX)-1 and -2 are constitutively expressed in the ciliary processes. COX-2 expression is reduced in primary open-angle and steroid-induced glaucoma. This is paralled by significantly lower PG concentrations in aqueous humor. These findings indicate a disturbance of the PG production in glaucoma. Defining the reason(s) for this may lead to a better understanding of the pathogenesis of this disease and to novel treatment approaches.
mAb Treatment of CNV
Choroidal neovascularization (CNV) is a major complication of age-related macular degeneration. Integrin avb3 is strongly expressed in vascular endothelial cells of surgically excised choroidal neovascular membranes and is thought to be a potential antigen for monoclonal antibody (mAb)-mediated drug targeting of CNV. Kamizuru et al. (p. 2664) report the efficacy of drug targeting mediated by anti-integrin avb3 mAb in a laser-induced CNV rat model. This suggests that mAb-mediated drug targeting may be beneficial in the treatment of CNV.
Pulsed Electron Avalanche Knife (PEAK)
Palanker et al. (p. 2673) describe an economical new instrument for precise, tractionless and "cold" cutting during intraocular surgery. PEAK uses a highly localized pulsed electric field rather than laser light as the means of tissue dissection. Micrometer-length plasma streamers in physiological medium accompanied by explosive evaporation of water in their vicinity cut soft tissue. The instrument made extremely precise cuts in retina, iris, lens and lens capsule without any evidence of thermal damage. The small delivery probe and modest cost make it promising for many ophthalmic applications, including retinal, cataract, and glaucoma surgery.
A Deficit in Dyslexia
Visual factors have historically played a significant role in causal theories of dyslexia. Simmers and Bex (p. 2737) have uncovered a consistent abnormality in the integration of visual information. The authors’ results suggest that individuals with dyslexia have poor perceptual organization, that is, the formation of a global precept from local features. This can be linked to reading where dyslexics will often suffer severe perceptual distortions (letters/words moving, doubling, reversing) when looking at a page of text, but encounter little difficulty in identifying a single letter or word when masked.
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