Yoram Solberg

The Association Between Cigarette Smoking and Ocular Diseases

Tobacco smoke is composed of as many as 4,000 active compounds, most of them toxic on either acute or long-term exposure. Many of them are also poisonous to ocular tissues, affecting the eye mainly through ischemic or oxidative mechanisms. The list of ophthalmologic disorders associated with cigarette smoking continues to grow. Most chronic ocular diseases, with the possible exception of diabetic retinopathy and primary open-angle glaucoma, appear to be associated with smoking. Both cataract development and age-related macular degeneration, the leading causes of severe visual impairment and blindness, are directly accelerated by smoking. Other common ocular disorders, such as retinal ischemia, anterior ischemic optic neuropathy, and Graves ophthalmopathy, are also significantly linked to this harmful habit. Tobacco smoking is the direct cause of tobacco-alcohol amblyopia, a once common but now rare disease characterized by severe visual loss, which is probably a result of toxic optic nerve damage. Cigarette smoking is highly irritating to the conjunctival mucosa, also affecting the eyes of nonsmokers by passive exposure (secondhand smoking). The dangerous effects of smoking are transmitted through the placenta, and offspring of smoking mothers are prone to develop strabismus. Efforts should be directed toward augmenting the campaign against tobacco smoking by adding the increased risk of blindness to the better-known arguments against smoking. We should urge our patients to quit smoking, and we must make them keenly aware of the afflictions that can develop when smoke gets in our eyes.

The role of intraocular lenses in anterior chamber contamination during cataract surgery.

Abstract · Background: Bacterial endophthalmitis is a rare vision-threatening disease, usually caused by microorganisms that are natural inhabitants of the eye lids and conjunctiva. This study was conducted to investigate the role of intraocular lenses (IOLs) in introducing bacterial contamination into the eye during cataract surgery and the efficacy of povidone-iodine solution in prevention this ocular inoculum. · Methods: Fifty patients underwent routine cataract surgery and intraocular lens implantation. One group of the patients was pretreated with external disinfection using povidone-iodine 4% before surgery, while the other group was only pretreated with saline irrigation. Before IOL implantation, a test IOL was placed on the conjunctiva and taken for microbiological studies. Anterior chamber tap was done at the beginning and at the end of each operation. Positive bacterial growth was followed by bacterial identification and sensitivity tests to various antibiotics. · Results: Bacterial growth was obtained in 14 of the 50 eyes (28%); in 5 eyes the organism was cultured from tapped aqueous and in 9 eyes from the test IOLs. Prophylactic use of povidone-iodine 4% solution effectively reduced the contamination rate from 34.7% to 16.7%. Coagulase-negative staphylococci were the most common organisms isolated (72%). Most organisms were sensitive to vancomycin (86%) and to fucidic acid (71%). There were no cases of clinical endophthalmitis. · Conclusions: IOLs are apparently potential vehicles for introduction of intraocular bacterial contamination. Instillation of povidone-iodine 4% into the cul-de-sac reduces the risk of bacterial inoculum. Vancomycin is the most effective single agent against intraocular contamination. In order to reduce potential intraocular contamination it is advisable to avoid contact between the IOL and ocular tissues.

Methylprednisolone Therapy for Retinal Laser Injury

OBJECTIVE Laser photocoagulation treatment of the posterior pole of the retina is often complicated by immediate visual impairment, which is caused by the unavoidable laser-induced destruction of the normal tissue adjacent to the lesion. A neuroprotective therapy aimed at salvaging this normal tissue might enhance the benefit obtained from treatment and permit safe perifoveal photocoagulation. To determine whether corticosteroids can provide neuroprotection during photocoagulation, we examined the effect of methylprednisolone on laser-induced retinal injury in a rat model. METHODS Argon laser lesions were inflicted on the retinas of 36 rats and were followed immediately by intraperitoneal injections of high-dose methylprednisolone or saline. The animals were sacrificed after 3, 20, or 60 days, and their retinal lesions were evaluated histologically and morphometrically. RESULTS No histopathologic differences were observed between the treated and control animals. Methylprednisolone treatment was demonstrated to posses some neuroprotective effect for a short time after laser exposure, but was ineffective in ameliorating the long-term results of retinal laser injury. CONCLUSIONS On the basis of our results, we suggest that high-dose methylprednisolone treatment is ineffective in ameliorating laser-induced retinal injury. Other drugs should be investigated for their potential role as neuroprotective agents to prevent the spread of retinal laser damage.

Treatment of laser-induced retinal injuries by neuroprotection

Retinal laser photocoagulation treatments are often complicated with immediate side-effect of visual impairment. To determine whether glutamate-receptor blockers can serve as adjuvant neuroprotective therapy, we examined the effect of MK-801, an NMDA-receptor antagonist, on laser-induced retinal injury in a rat model. Argon laser retinal lesions were created in the retina of 36 DA rats. Treatment with intraperitoneal injections of MK-801 or saline was started immediately after the laser photocoagulation. The animals were sacrificed after 3, 20 or 60 days and the retinal lesions were evaluated histologically and morphometrically. Photoreceptor-cell loss was significantly smaller in MK-801-treated rats than controls. The proliferative membrane composed of retinal pigment epithelial cells which was seen at the base of the lesion in control retinas, was smaller in the MK-801-treated retinas. MK-801 exhibited neuroprotective and anti-proliferative properties in the retina. Glutamate-receptor blockers should be further investigated for serving as adjuvant therapy to retinal photocoagulation treatments.

Effect of corticosteroids on healing of the corneal endothelium in cats

Abstract• Background: Anterior segment surgery is frequently complicated by damage to the corneal endothelium. We examined the effects of corticosteroids, which are widely used for the suppression of postoperative inflammation, on the process of endothelial cell regeneration. • Methods: The effect of corticosteroids on healing of the corneal endothelium was examined in 10 domestic cats. In both eyes a circular area, 8 mm in diameter, was scraped off at the center of the corneal endothelium without damaging Descemets membrane. Immediately after scraping, as well as 2 and 5 days later, each animal received a unilateral retrobulbar injection of betamethasone sodium phosphate (2 mg). The other eye served as a control and received a retrobulbar injection of the vehicle only. • Results: Evaluation of the corneal endothelium 2, 5 and 7 days after the trauma revealed that relative to the control contralateral eyes, the corticosteroid-treated eyes exhibited a higher mean coefficient of variation of the corneal endothelium cell area, fewer hexagonal cells, a larger number of polygonal cells with 3, 4, 7 and 8 cellular facets, thinner corneas and less inflammation. • Conclusions: These findings suggest that corticosteroids unfavorably affect the regeneration of corneal endothelial cells after injury. As corticosteroids appear to have both positive and adverse effects on corneal function after trauma, they should be used with caution.

Neuroprotective therapy for argon-laser-induced retinal injury

Laser photocoagulation treatment of the central retina is often complicated by an immediate side effect of visual impairment, caused by the unavoidable laser-induced destruction of the normal tissue lying adjacent to the lesion and not affected directly by the laser beam. Furthermore, accidental laser injuries are at present untreatable. A neuroprotective therapy for salvaging the normal tissue might enhance the benefit obtained from treatment and allow safe perifoveal photocoagulation. We have developed a rat model for studying the efficacy of putative neuroprotective compounds in ameliorating laser-induced retinal damage. Four compounds were evaluated: the corticosteroid methylprednisolone, the glutamate-receptor blocker MK-801, the anti-oxidant enzyme superoxide dismutase, and the calcim-overload antagonist flunarizine. The study was carried out in two steps: in the first, the histopathological development of retinal laser injuries was studied. Argon laser lesions were inflicted in the retinas of 18 pigmented rats. The animals were sacrificed after 3, 20 or 60 days and their retinal lesions were evaluated under the light microscope. The laser injury mainly involved the outer layers of the retina, where it destroyed significant numbers of photoreceptor cells. Over time, evidence of two major histopathological processes was observed: traction of adjacent nomral retinal cells into the central area of the lesion forming an internal retinal bulging, and a retinal pigmented epithelial proliferative reaction associated with subretinal neovascularization and invations of the retinal lesion site by phagocytes. The neuroprotective effects of each of the four compounds were verified in a second step of the study. For each drug tested, 12 rats were irradiated wtih argon laser inflictions: six of them received the tested agent while the other six were treated with the corresponding vehicle. Twenty days after laser expsoure, the rats were sacrificed and their lesions were subjected to image-analysis morphometry. The extent of retianl damage was assessed by measuring the lesion diameter and the amount of photoreceptor cell loss in the outer nuclear layer. Methylprednisolone and MI-801 were shown to ameliorate laser-induced retinal damage, whereas both superoxide dismutase and flunarizine were ineffective. Furthermore, MK-801 diminished the proliferative reaction of the retinal pigment epithelial cells. On the basis of our results we suggest that the pigmented rat model is suitable for studying and screening various compounds for their neuroprotective efficacy in treating retinal laser injury. We further suggest that glutamate might play a key role in mediating retinal injury induced by laser irradiation.

Effects of methylprednisolone on laser-induced retinal injuries

Methylprednisolone have been demonstrated to ameliorate retinal photic injury. In the current study we examined its effect on laser induced retinal injury. Retinal lesions were inflicted by argon laser in 36 pigmented DA rats. The treated groups received intra-peritoneally methylprednisolone in saline, injected 3 times a day for 2 days, starting immediately after exposure. The controls received the vehicle on the same schedule. The rats were sacrificed 3, 20 or 60 days after laser exposure and the lesions were evaluated by light microscopy and morphometric measurements. Laser injuries were associated with disruption of the outer retinal layers. Three and 20 days after exposure, the loss of the photoreceptor-cell nuclei was significantly milder in the treated groups as compared with controls. There was no difference 60 days after exposure. In conclusion, methylprednisolone reduced temporarily the photoreceptor cell loss in argon laser induced retinal injury, when treatment was started immediately after laser exposure. There was no long term effect.

Pharmacological treatment of laser eye injuries by neuroprotection

Many retinal injuries result in an irreversible neuronal loss, which can not yet be reduced by pharmacological methods. To determine whether glutamate-receptor blockers can serve as neuroprotective agents in the retina, as they do in the central nervous system, we examined the effects of MK-801, an NMDA-receptor antagonist, on laser-induced retinal injury in a rat model. Immediately and 8 h after argon laser retinal photocoagulation, rats were treated with intraperitoneal injections of MK-801 (3 mg/kg) or saline. After 3, 20 or 60 days the animals were sacrificed and their retinal lesions were evaluated histologically and morphometrically. Photoreceptor cell loss, both immediately and up to 2 months after laser irradiation, was significantly smaller in MK-801-treated rats than controls. MK-801 exhibits neuroprotective property in the retina. This points to the involvement of glutamate in the laser-induced retinal neuronal damage. Glutamate-receptor blockers should be further investigated for therapy of retinal diseases characterized by neuronal cell destruction.