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abstracts Edited by C. William Simcoe, M.D.

As cataract and intraocular lens implant surgeons, we concern ourselves largely with the structural and mechanical considera­tions of ophthalmology, such as corneal endothelial cell counts, in­traocular lens design, and surgical procedures. In fact, lens im­plantation has improved the overall quality of cataract surgery by stimulating the development of precision microsurgical instru­mentation and techniques. Such refinement of new and existing skills will no doubt continue, but I believe we will also see much greater emphasis on research in such basic parameters as immu­nology, enzymes and other chemical mediators, cellular ultrastructure and physiology. Some evidence of the incredible proliferation oflaboratory and clinical research can be found in the April 1980 supplement to Investigative Ophthalmology and Visual Science, which contains abstracts of over 1,000 presentations made at the meeting of the Association for Research in Vision and Ophthalmology (ARVO) held in Orlando, Florida, in May of this year. The following overview gleaned from these abstracts sum­marizes just a few of the very interesting things being done.

Kinoshita et al: Blocking sugar cataract formation with Sorbinil. The common factor which triggers the events leading to sugar cataracts is aldose reductase (AR), the enzyme that converts sugars to polyols. Support for this concept comes from experi­ments in which AR inhibitors delayed cataract formation in galactosemic rats and diabetic dogs. Recent studies with more po­tent AR inhibitors further support the polyol hypothesis. Sorbinjl is an inhibitor which alters the course of diabetic cataracts in rats. Lens changes in the form of equatorial vacuoles appeared within three weeks of diabetes, while the development of a dense nuclear opacity required six to ten weeks. Diabetic rats treated orally with Sorbinil did not develop any lens changes during six months of ob­servation. Sorbinil treatment did not alter the blood sugar level, which was in the 500 mg% range. Prior to the cataract the lenses of the untreated diabetic group had a sorbitol level 25 times that of the treated group. The course of cataract formation in galactose­fed rats was also strikingly blocked by Sorbinil treatment. Lenses of galactosemic rats developed vacuoles in three days and dense nuclear opacity within two weeks. However, with Sorbinil treat­ment, no lens changes were observed in four months. These re­sults indicate that potent AR inhibitors not only delay but can pre­vent the formation of sugar cataracts.

Kador et al: Anti-allergy drugs as aldose reductase inhibitors. The enzyme aldose reductase, found in the lens and other tissues, appears to be the key factor in initiating the cataractous process in galactosemic and diabetic animals. This enzyme has also been im­plicated in other diabetic complications. Active aldose reductase inhibitors may act by accepting or complexing a pair of electrons from aldose reductase at a site independent of the substrate or NADPH site, a mechanism of action which is similar to that postu­lated for anti-allergy compounds. Various anti-allergy compounds, including representatives of the quinoline, pyrido (3,2-g) quino­line, pyrido (2, I-b) quinoline, oxanilic acid, isoxazole and couma­rin class, are potent aldose reductase inhibitors which compare fa­vorably with Sorbinil.

Varama et al: Photoperoxidation in rat lens; preventive mecha­nisms. Studies suggest that photodamage to the ocular lens may involve continuous photocatalytic generation of superoxide radi­cals during photopic vision. Rat lenses incubated in medium generating superoxide radicals lose photochemical clarity. The light-induced damage appears to implicate photoperoxidation of lipids. Damage is substantially inhibited by superoxide in dismutase and catalase, suggesting that the process is initiated by the generation of O2- and its derivatives. Glutathione and ascorbate both significantly protected against the peroxidative process.

Spector et al: H20 2 and human cataract. Recent observations have established that oxidation of human lens membrane proteins

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precedes the development of lens opacity and that marked oxida­tion of most protein constituents occurs with cataract formation. One of the possible compounds that may cause such oxidation is H20 2. The level of hydrogen peroxide in human lenses and corre­sponding aqueous humor was measured, using donors ranging from two to 74 years of age. The aqueous fluid was obtained immediately before cataract extraction or after enucleation. Eyes containing senile cataracts had significantly elevated H20 2 levels.

Kulkarni and Srinivason et al: Effects of topical and intraperitoneal indomethacin and flurbiprofen on prostaglandin (PC) biosynthesis of rabbit anterior uvea. Increased levels of PCs are found in the aqueous of experimental animals and patients with anterior uveitis. Using rabbit anterior uvea, it has been dem­onstrated that indomethacin inhibits conversion of arachidonic acid into PC products in vitro, however the effectiveness of indomethacin in vivo has not been studied. Topical or intraperitoneal indomethacin pretreatment inhibited PC forma­tion from arachidonic acid in the rabbit anterior uvea. The inhibi­tory effects of indomethacin and flurbiprofen lasted for at least six hours following pretreatment.

Zimny et al: Effects of soft contacts on long-term corneal wound healing in rabbits. Corneal lesions 7.5 mm in diameter and 0.2 mm in depth were made with an ocular trephine in both eyes of rabbits. The right eyes were not treated; Sofcon lenses were placed on the left eyes. Sutures were placed both medially and lat­erally through the lids of both eyes. The time periods studied were 120 and 170 hours. Both eyes at both time periods showed varying patterns of corneal epithelial cell coverage. It was quite apparent, however, that the more normal appearing epithelial surface was on the eyes that had been covered with contact lenses. Uncovered eyes showed nonuniform cell populations with curled, shredded cell margins. The microvilli were not distinct and cra­ters were frequently seen. Covered eyes showed more uniform populations of cells, with good cell contact and attachment. Soft contact lenses appeared to have an advantageous effect on restoring a relatively normal epithelial surface following a corneal lesion in rabbits.

Arzeno and Miller: Effect ofNa-hyaluronate on corneal wound healing. Because of the use of Na-hyaluronate (Healon) for endo­thelial protection during anterior segment surgery, its effect on corneal wound healing was studied. Corneal incisions were made in both eyes of 14 albino rabbits. Na-hyaluronate was used to fill the anterior chamber of the test eye, and balanced salt solution was used in the control eye. The wounds were sutured with 10-0 nylon. On the seventh postoperative day, wound strength was measured. After suture removal, intraocular pressure was in­creased until the wound burst. Results showed no significant dif­ference in wound strength between the test eye and the control eye.

Chan et al: Culture of corneal cells using a new cell isolation technique. A new technique has been developed which permits nearly complete and quantitatively reproducible recovery of rab­bit corneal epithelial (EP), fibroblast (SF) and endothelial (EN) cells by injecting saline into the stroma to split the cornea into an anterior half containing EP and SF and a posterior half containing SF and EN. After collagenase treatment, EN and EP layers were completely peeled off the stroma by microdissection. SF cells were isolated from the remaining stroma by centrifugation, after digestion of the collagen fibers for an additional two hours at 37°. The purity of each cell type obtained was confirmed by light mi­croscopic monitoring at each step. Cultures of these three cell types showed distinctly different growth patterns, ultrastructure and biochemical compositions. Electron microscopy revealed that cultured corneal cells contained many in vivo structural character­istics.

Hessburg: Efforts to reduce astigmatism follOWing penetrating keratoplasty. Postoperative astigmatism might be reduced in pen-

etrating keratoplasty if surgeons could cut a straight-sided round hole in the recipient cornea and place in that hole a round donor button which also had straight sides. If the donor button precisely fit the recipient hole, sutures placed loosely enough to minimize deformation of collagen tissue without sacrificing a water seal might also reduce warping of the transplant and its cradle. A dis­posable trephine which helps the surgeon cut a straight graft has a suction ring which supports the cornea 0.5 mm outside the tre­phine blade, making it possible for the surgeon to lift up the cor­nea as the blade passes through the corneal tissue. It also has a tre­phine blade, 0.04 mm in thickness (currently available razor blades are 0.1 mm to 0.2 mm thick; the "super" razor blades are 0.1 mm thick) with a honing angle of 8° (the usual razor blade has a honing angle of 14°). This trephine makes a straight-sided cut through corneal tissue.

Eiferman and Wilkins: The effect of air on the corneal endothe­lium. Intraocular lens implantation is associated with a greater en­dothelial cell loss than conventional cataract extraction. A large air bubble has been advocated as a cushion to protect corneal endo­thelial cells during lens implantation, however the use of air has been shown to cause abnormalities in rabbit endothelium. In 15 patients undergoing routine cataract surgery, a large air bubble was allowed to fill the anterior chamber after lens delivery and was left in the eye. The pupil was constricted to prevent bubble migra­tion behind the iris. In a controlled group of patients the anterior chamber was reformed with balanced salt solution. Pre- and post­operative endothelial cell counts were taken. The control group had an 8% loss, whereas the patients whose anterior chambers were filled with air had an 18% loss. In addition, some of the pa­tients in the latter group developed a transient postoperative peau d' orange appearance (pseudo-guttata) of the corneal endothelium. Use of air in the anterior chamber may contribute to cell loss dur­ing operative procedures.

Feman and James: Idiopathic macular holes. Idiopathic macu­lar holes in association with focal retinal detachments were stud­ied in 24 eyes. Cystoid retinal changes were not identified at the margins of these retinal holes. Posterior vitreous separation was not present in every eye with a macular hole. Fluorescein angiographic tests failed to reveal retinal vascular abnormalities. Twenty of the eyes were in female patients and most of these pa­tients had been on systemic estrogen therapy before the onset of their visual symptoms.

Kramer: Cystoid macular edema (CME) in penetrating kerato­plasty (PKP). Aphakic PKP (APKP) and combined PKP with lens extraction (CPKP) are highly successful surgical procedures, with a 90% rate of clear corneas. The macula does badly however and visual acuity is disappointing, principally because of CME or pre­existing macular degeneration. In an attempt to determine wheth­er vitreous manipulation at the time of surgery alters the macular outcome, 132 patients were studied prospectively. All with pre­existing aphakia had anterior vitrectomy at the time of APKP. Those planned for CPKP were randomly assigned to one group which had anterior vitrectomy or to a second group which had no vitrectomy at the time ofCPKP. The incidence of clinically signifi­cant CME was 42% in APKP eyes, 19% in CPKP eyes, 33% in CPKP eyes with vitrectomy, and 4% in CPKP eyes without vitrectomy. The data suggest strongly that transpupillary anterior vitrectomy at the time ofPKP, as compared to no vitreous manip­ulation at all, may contribute to a high incidence of postoperative CME.

Beebe et al: PUrification oflentropin, a factor in vitreous hu­mor which promotes lens fiber cell differentiation. Lens fiber cell differentiation is controlled by a factor present in the posterior part of the eye. This activity is associated with lentropin, a glyco­protein of approximately 60,000 MW. Complete purification of lentropin should provide information on the structure, tissue of origin and mechanism of action of a substance which is important

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in controlling lens shape and exerts direct control over lens cell differentiation.

Wenk: Specific binding of 3H-dexamethasone in bovine lens. Localization of specific binding sites for 3H-dexamethasone in bo­vine lens material was carried out using a dry autoradiographic method suitable for diffusable substances, such as glucocorticoids. The nuclei of lens fibers in the bow regions showed distinct locali­zation of autoradiographic grains. The nuclei of cells in the anteri­or epithelium were also labeled. Lens fiber in the cortex and in the lenticular nucleus showed diffuse label with no special rela­tionship to membranes or to position along the length of the fiber. The capsule demonstrated a paucity of label in both anterior and posterior regions. These observations are consistent with previous biochemical data demonstrating specific glucocorticoid receptors in lens epithelium and the absence of specific localization in other regions of the lens. The data indicate that lens epithelial cells are target cells for glucocorticoids and that glucocorticoid-related pos­terior subcapsular cataracts may represent a genomic response to these steroids.

Hodapp et al: The effect of topical Clonidine on intraocular pressure. Topical 0.125% and 0.25% Clonidine was compared to 2% pilocarpine and placebo in a randomized double-masked study of 20 symmetric ocular hypertensive subjects. After an initial dose of each drug to one eye, intraocular pressure, pupil diameter, vis­ual acuity, blood pressure, and pulse rate were measured over 24 hours. The subjects then used the medication three times daily to one eye, and the diurnal measurements were repeated one week later. When compared to placebo-treated eyes, 0.125% Clonidine lowered lOP substantially for more than eight hours. lOP re­sponse to 0.25% Clonidine was greater and longer lasting than that produced by 0.125% Clonidine. Clonidine (0.25%) substan­tially decreased lOP in the untreated fellow eye.

Tano and Machemer: Experimental intravitreal steroid therapy of intraocular proliferation. Autotransplantation of tissue­cultured skin fibroblasts into the vitreous cavity of rabbit eyes causes intravitreal strand formation, traction retinal detachment and neovascularization of the retina. Following a single intravitreal injection of 1 mg Triaminolone-acetonide only 15(34%) of 44 eyes developed traction retinal detachments, compared to 36(84%) of 43 untreated eyes. Five(11 %) of 44 treated eyes devel­oped neovascularization, compared to 29(67%) of 43 untreated eyes. The differences are highly significant. Intraocular steroid therapy will hopefully be of help in the treatment of human prolif­erative diseases.

Prchal et al: Diabetes and cataract formation. A prospective, double-masked study was undertaken to evaluate the relationship of diabetes mellitus to cataract formation. A group of 213 male dia­betic patients was compared to an age and sex-matched control group. Lens changes were divided into nine grades based on visu­al significance; posterior subcapsular (PSe) changes were consid­ered as a group as well as separately. Diabetes is associated with PSC and other significant cataracts, but is less cataractogenic than age or steroids.

Skalka and Prchal: Effect of cortical steroids on cataract f01ma­tion in men. While the cataractogenic effects of cortical steroids in men are beyond dispute, there is disagreement in the literature concerning the effects of total dosage, intensity of dosage and du­ration of administration. In a group of 106 male patients the differ­ence in PSC cataract incidence among those with and without a history of cortical steroid therapy was statistically significant, how­ever there was no significant correlation between PSC cataracts and total steroid dosage, weekly dosage (intensity), duration of dosage, or age of patient. Some recent literature suggests that the most important factor in steroid-induced cataract formation may be variability in individual susceptibility to the side effects of cor­tical steroids. Findings of this study support this contention and suggest abandoning the concept of a "safe" dosage level. All pa-

tients receiving cortical steroid therapy are at risk of cataract for­mation, and there are no current means of predicting which pa­tients will develop steroid-induced cataracts.

***** Krejci (Glaucoma 2:259, 1980) describes a hydrogel capillary drain (HCD) for permanent microdrainage of the anterior cham­ber in glaucomatous eyes. The thin, flat implant is a monomer mixture of hydroxyethylmethacrylate, glycerol and a polymeriza­tion catalyst, and is perforated by regular capillaries running par­allel to each other. Drainage can occur through the material and through the O.I-mm lumina of the capillary system. The implant is inserted under a broad limbus-based conjunctival flap through a limbal incision and is anchored to the sclera by a suture under­neath the flap. Immediate swelling of the HCD plugs the incision, promoting restoration of the anterior chamber. This implant was used in 34 cases of advanced or absolute primary or secondary glaucoma, most of which were painful and even hemorrhagic. In­tensive conservative and frequently repeated surgical treatment had failed. Ages ranged from five months to 82 years, with amean of 62 years. During a follow-up period of six to nine years, 26 of these patients achieved permanent success with normalization of intraocular pressure, disappearance of corneal edema, and sup­pression of pain. Three had decreased but not permanently nor­malized lOP, disappearance of corneal edema and relief from pain. The operation failed in five patients. The best results were achieved in cases of open-angle glaucoma. The mean pre-op lOP was 63 mm Hg; the mean lOP during the follow-up period was 20 mm Hg. Permanent contact of the HCD with corneal endotheli­um, iris, or lens capsule did not lead to iris atrophy, cataract de­velopment or corneal endothelial dystrophy. In no case was the HCD eliminated spontaneously, nor did it cause irritation or in­flammatory reaction of the uvea.

Mehta (Trans Ophthalmol Soc UK 99:183, 1979) describes clin­ically detectable biodegradation of nylon IOL loops in 11 eyes of seven children and four adults who had undergone secondary im­plantation of iris clip or iridocapsular implants. Loop degradation did not produce uveitis, keratopathy, or IOL instability in any of these patients. Two children with iris clip lenses had unilateral glaucoma in the implanted eye. One of these eyes also had dense amblyopia and the IOL was removed at the time of trabccu­lectomy. Scanning electron microscopy (SEM) of the loops showed extreme attenuation with superficial transverse cracking and fissuring and deeper fibrillary structure or waves of erosion. The optical portion (Perspex CQ) showed no evidence of degrada­tion, even at the limit of SEM resolving power. A search for nylon particles in the trabeculectomy specimen of the second child yielded strongly birefringent particles in the trabecular tissue.

Jain and Batra. (Ind ] Ophthalmol 11:26, 1979) produced high aqueous concentrations of dexamethasone sodium phosphate in patients who had worn Sauflon 70 lenses soaked in this drug for 30 minutes and removed immediately before cataract surgery. These high concentrations persisted up to four hours but were lower and less sustained than those achieved by subconjunctival injection of dexamethasone sodium phosphate. In milder cases of anterior chamber inflammation this modality offers certain advantages.

Cheng et al: (Trans Ophthalmol Soc UK 99:321, 1979) discuss the mechanisms of corneal endothelial cell loss after lens implan­tation and report the results of dipping lens implants in serum prior to implantation in rabbits and humans. The significant de­crease in cell loss by this method suggests that seruITI is more ef­fective than plasma, albumin, tissue culture fluid or Ringer's solu­tion in protecting the endothelium.

Treumer (Klin Nbl Augenh 175:811, 1979) reports on the use of permanent-wear silicone contact lenses in 114 aphakic eyes (55 children, 59 adults) with up to two years of follow-up. If they were fitted correctly, these lenses were well tolerated for suprisingly

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long periods of time. Two cases in this series had a superficial ulcer and three cases had a circumscribed corneal infiltration . There was no corneal vascularization . Postoperative vision was good: corneal astigmatism was reduced b y an average of 0.87D. The main problems were deposition of organic material and, in some cases, poor lens hydrophilicity. Constant lens mobility is es­sential for long-term lens tolerance without complications. At present, it is recommended that the use of permanent wear sili­cone lenses be restricted to special indications. . Brewitt (Acta OphthalmoI57:945, 1979) used scanning electron

microscopy to examine morphological changes and re­epithelialization in the rabbit cornea following linear incision and central keratectomy. After rounding off and retraction of wound edges during the first six hours, the stroma was infiltrated by leukocytes. Superficial epithelial cells migrated over the edges of the · wound to protect the· exposed cleft in the tissue. After 15 hours, basal epithelial cells sent pseudopod-like processes of vary­·irig lengths into th~ wound area, followed by subsequent cell lay­ers. Three types of cells could be distinguished: 1) very flat cells with smooth edges and no microprojections, which adapted their shape to the clefts in the damaged stroma; 2) flat cells with folded surface-level plasma membrane which gave these cells a coral-like appearance; and 3) cells with voluminous cytoplasmic processes . The rapidly sliding epithelium covered the defect with star­shaped growths so that after only 48 hours the wound was almost completely closed. After 96 hours , the deep wound was complete­ly covered by epithelium. These early epithelial cells had demon­strably fewer microvilli and microplicae than normaL Only after a minimum of five days could the normal surface relief be seen. The surface cells dominated the first stage of the healing process and

. the basal cells dominated the second stage. Using clinical specular microscopy, Setala (Acta Ophthalmol

57:1004, 1979) reports corneal endothelial cell counts in 25 pa­tients with unilateral acute glaucoma attacks. In most cases, pe­ripheral iridectomy was performed on the affected eye and pro­phylactically on the fellow eye. Intraocular pressure elevations lasting three days or more lowered central endothelial cell densi­ty, however pressure elevations lasting up to two days did not af­fect endothelial cell count. Operative glaucoma procedures de­creased central endothelial cell density by approximately 4.8%. There was a clear correlation between the duration of elevated pressure and the number of centraLcorneal endothelial cells lost.

Jerndal and Anders (Acta Ophthalmol 57:826, 1979). By stud­ying both the glaucomatous and nonglaucomatous members in af­flicted pedigrees it has been established that the premorbid gonio­genesis, inherited in an autosomal dominant mode, plays a deci­sive role in the eventual development of open-angle glaucoma. Goniodysgenesis has been documented not only in infantile con­genital glaucoma but also in late congenital glaucoma (often misin-

terpreted as glaucoma simplex) and in families with pigmentary glaucoma and exfoliation glaucoma. In addition , there is evidence that goniodysgenesis is the morphological prerequisite of the high pressure elevation secondary to use of topical steroids. Valid con­clusions from studies of glaucoma pedigrees assume completion of the following: 1) search for and attempted definition of the pri­mary genetic trait; 2) examination of all family members, glauco­matous as well as non glaucomatous, with regard to genetic trait; 3) definition of the criteria for glaucoma diagnosis; and 4) gonioscopic classification of the type of glaucoma .

Pandolfi and Lentz (Exp Eye Res 29:563, 1979) report partial purification and characte rization of keratokinase, the fibrinolytic activator of the cornea. Keratokinase (KK) is a fibrinolytic enzyme found in corneal cultures . KK converts plasminogen into plasmin by a limited proteolytic pattern identical to that of urikinase, the urinary activator. The molecular weight of KK is around 55,000 daltons, in the same range as that of urikinase. KK also shows a similar biphasic activity response to increasing concentrations of epsilon aminocaproic acid and is minimally bound to fibrin during clotting. KK may playa role in a number of pathophysiological states of the cornea, such as corneal swelling, inflammation and· collagen metabolism .

Kairns (Boll di Oculistica 58:243, 1979). Neovascular glaucoma occurs most often with diabetic retinopathy and following central retinal vein occlusion , notably the ischemic response type. Neovascular glaucoma is less frequently associated with uveal melanoma, central retinal artery occlusion, internal carotid artery stenosis , caroticocavernous fistula, or following closed vitrectomy procedures. Pressure e levation is caused by development of a fibrovascular membrane over the internal trabecular surface . As this membrane draws the iris toward the posterior corneal surface, peripheral anterior synechiae create secondary block. Newly formed vessels are concentrated near the pupillary margin and on that part of the iris proximal to the trabeculum. Therapeutic drain­age procedures have a very low success rate because ordinary drainage fistula are blocked by the fibrovascular membrane. De­pressing aqueous output lowers aqueous turnover and therefore use of acetazolamide , timolol and cyclodestructive procedures could theoretically exacerbate neovascularization . On the other hand, cyclocryotherapy may decrease the ciliary body's produc­tion of "vaso-formative factor". Goniophotocoagulation appears to temporarily prevent new vessels from closing the angle; however, unlike retinal photocoagulation, this procedure does not seem to reduce formation of the vaso-formative factor. The most rational therapy for neovascular glaucoma is the long tube implant of Moltini. By increasing aqueous outflow, this method controls ex­isting hypertension and causes rapid evacuation of the vaso­formative factor, thus decreasing the stimulus for further neo­vascularization.

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