Lens capsule opacification in aphakic and pseudophakic eyes.

BACKGROUND: Posterior capsule opacification (PCO) is the most common complication of lens extraction. Although intraocular lenses (IOLs) are thought to inhibit capsule opacification, the mechanisms by which they do this are poorly understood. This study was done to determine the effects of pseudophakia on secondary cataract and PCO in experimentally lentectomized dogs. METHODS: Twenty-four normal dogs were bilaterally lentectomized by phacoemulsification and unilaterally implanted with a plano-convex polymethylmethacrylate IOL. Secondary cataracts and capsule opacification were evaluated at weeks 1, 2, 4, 10, 14, and 20 after surgery by retrolillumination photography, light microscopy, and scanning and transmission electron microscopy. RESULTS: The pattern of secondary cataract and PCO in dogs was found to be similar to that in other animal species. Production of new lens material was prominent in the equatorial region, and PCO resulted from fibrous metaplasia of lens epithelium and subsequent capsular fibrosis and wrinkling. The presence of an IOL did not prevent the posterior migration of epithelium, nor did it prevent fibrous metaplasia. The presence of an IOL did, however, minimize the capsule-wrinkling effects of fibroplasia and limit the space available for lentoid formation. CONCLUSION: In pseudophakic eyes, IOLs influence secondary cataract formation by limiting the space available for lentoid formation and by maintaining a linear scaffolding for lens epithelial fibrous metaplasia.

Inhibition of proliferating lens epithelium with antitransferrin receptor immunotoxin.

We investigated the effect of an antitransferrin receptor immunotoxin (454A12-rRA) on proliferating human and baboon lens epithelium in vitro. Human and baboon lens epithelial cells grown in modified TC-199 medium at 35 degrees Celsius in 7% CO2 were seeded in 24 well plates at a density of 17,500 cells/ml to 40,000 cells/ml. The cells were exposed to various concentrations of 454A12-rRA for seven days. The sensitivity of proliferating human lens epithelium to 454A12-rRA was dependent on the dose, with a 60% to 70% reduction in cell counts at immunotoxin concentrations of 100 ng/ml and above. The immunotoxin had no significant effect on baboon lens epithelium in vitro, which suggests that it is specific for human tissue. By preventing the proliferation of human lens epithelial cells, immunotoxin 454A12-rRA may be useful in the management of posterior capsule opacification after planned extracapsular cataract surgery.

Suppression of human corneal epithelial proliferation with breast carcinoma immunotoxin.

We examined the effects of the immunotoxin 260F9 Mab-recombinant ricin A (developed against human breast carcinoma) on proliferating and confluent human corneal epithelium (HCE) cells in vitro. HCE cells derived from explants of discarded human donor corneoscleral rims were established as proliferating and confluent cell cultures, and were exposed continuously for 7 days to immunotoxin. Final cell counts at day 7, and thymidine uptake measured at days 1 and 7 postexposure, showed > 95% suppression of proliferating cells at an immunotoxin concentration of 10 ng/ml, with confluent HCE cells relatively unaffected. This immunotoxin may prove useful in treatment of proliferative ocular epithelial diseases such as epithelial downgrowth or squamous cell carcinoma of the ocular surface.

Ultrastructure of fiber cells and multilamellar inclusions in experimental diabetes.

PURPOSE: The goal of this ultrastructural study was to examine fiber cell shape and intercellular junctions during the early stages of fiber cell breakdown and edema in diabetic rabbit lenses. METHODS: Lens abnormalities were recorded with a slit lamp. Between 6-10 mo after drug treatment, diabetic lenses and untreated control lenses were freshly enucleated and sectioned with a vibrating knife microtome. The thick tissue sections were chemically fixed and processed for thin-section electron microscopy. RESULTS: Alloxan-induced diabetes in albino rabbits produced clinically apparent cataracts as soon as 1 mo after the animals became hyperglycemic. The cataracts displayed cortical fluid-filled vacuoles in the equatorial region and at the cortex-nucleus interface, white specks scattered throughout the cortex, and posterior subcapsular cataracts. Fiber cells just deeper than the large cortical vacuoles had oval or spindle-shaped cross sections. Multilamellar inclusions, not reported previously for diabetic lenses, were observed at or near the fiber cell interfaces and were composed of concentric or spiral rings of plasma membrane-bound cytoplasmic processes. Undulating membranes were present throughout most of the multilamellar inclusions. Transparent lenses from untreated controls did not have such multilamellar bodies or extensive membrane undulations in cells at the same distance from the lens surface. CONCLUSIONS: Fiber cells respond to the diabetic insult differently depending on their stage of differentiation and age. The observed changes are consistent with the hypothesis that hyperglycemia accelerates the formation of age-related changes in fiber cells.

Analysis of corneal and conjunctival microenvironments using monoclonal antibodies.

PURPOSE: The authors phenotypically compared epithelial and nonepithelial components of human corneal and conjunctival microenvironments using a panel of monoclonal antibody reagents that included markers of epithelial cell maturation, markers of mesodermal-derived fibrous tissue and vessels, markers of specific keratins, and markers of major histocompatibility complex Class I and II antigens. METHODS: Corneoscleral rims obtained after trephination of the donor button for use in penetrating keratoplasty procedures were studied. RESULTS: A comparison of cornea and conjunctiva with anti-epithelial and antikeratin antibodies demonstrated that corneal and conjunctival keratinocytes undergo similar antigenically defined pathways of maturation. However, the reactivity of antibody 12/1-2 (antibody against low molecular weight keratins) with conjunctival but not corneal basal cells suggested differences in keratin expression between the two epithelial types. Using antibodies against major histocompatibility complex Class I and II antigens, it was demonstrated the two tissues were similar with Class I determinants found on all epithelial, stromal, and endothelial cells, and Class II determinants found on Langerhans' cells, vessels, and a subset of stromal cells. CONCLUSIONS: The availability of tissue-specific markers of epithelial and nonepithelial components of the cornea and conjunctiva should be of use in the study of the roles the ocular microenvironment might play in the pathogenesis of ocular inflammatory diseases.

Acyclovir-resistant herpes simplex virus keratouveitis after penetrating keratoplasty.

PURPOSE: A case of acyclovir-resistant herpes simplex virus keratouveitis after penetrating keratoplasty is reported. METHODS: Resistance to acyclovir was evident clinically and was confirmed by in vitro susceptibility testing. The susceptibility of the herpes simplex isolates to acyclovir and foscarnet was determined by a dye uptake assay that measured cytopathic effect, and thymidine kinase activity was measured by a plaque autoradiography technique. RESULTS: The viral isolate from postoperative day 22 was susceptible to acyclovir and foscarnet, and showed normal thymidine kinase activity. Isolates from postoperative days 29 and 32 (coinciding with deterioration in clinical appearance) were resistant to acyclovir, susceptible to foscarnet, and deficient in thymidine kinase activity. CONCLUSION: Practitioners should be aware of the potential for the emergence of resistance in this setting; prophylaxis and rational alternate therapies are discussed.

Cellular architecture in age-related human nuclear cataracts.

Age-related or senile human nuclear cataracts were examined using electron microscopy of thin sections prepared from thick vibrating-knife microtome sections of nuclei extracted by extracapsular surgery. The use of extended aldehyde-tannic acid fixation of 80-120-microns thick vibrating-knife microtome sections overcame the difficult problem of preserving the hardened nuclear core of aged lenses. Comparisons were made between a typical nuclear cataract, containing a central opacity and a transparent rim, and a more advanced, or mature, completely opaque nuclear cataract. The typical nuclear cataract contained no obvious cell disruption, cellular debris, or objects that readily could explain the central opacity. The fiber cells had intact uniformly stained cytoplasms with well-defined plasma membrane borders and gap junctions. The transparent rim and the nuclear core appeared similar, except that fiber cells in the nucleus were more condensed with more elaborate intercellular interdigitations. The mature cataract showed various types of cell disruption in the perimeter but not in the core of the nucleus. These disruptions were globules, vacuoles, multilamellar membranes, and clusters of highly undulating membranes. Because these potential scattering centers were not found in the nuclear core, they probably were not the sole cause of the observed opacity. Other potential scattering centers found throughout the mature cataract nucleus included variations in staining density between adjacent cells, enlarged extracellular spaces between undulating membrane pairs, and protein-like deposits in the extracellular space. Similar features, although less pronounced, were present in the typical nuclear cataract. It was concluded that massive cell disruption is not essential to the formation of a central nuclear opacity. Subtle structural changes, especially small fluctuations in protein density between adjacent cells and alterations of the membranes and the extracellular space, probably contribute significantly to the central opacities in human nuclear cataracts.

Inhibition of human corneal epithelium with immunotoxin 454A12-rRA.

We examined the effects of the immunotoxin 454A12-rRa on proliferating and confluent human corneal epithelium (HCE) in vitro. Proliferating HCE was sensitive to 454A12-rRA in a dose-dependent fashion. At immunotoxin concentrations of 1,000 ng/ml for 7 days we observed an 86% reduction in cell counts. Confluent HCE was not sensitive to 454A12-rRA at equivalent concentrations of immunotoxin. These data confirm previous observations regarding selective sensitivity of proliferating ocular tissue to immunotoxin, but suggest that HCE is less sensitive to 454A12-rRA than other ocular cell types.

Treatment of contact lens-related ocular surface disorders with autologous conjunctival transplantation.

The authors describe two cases of chronic ocular surface disorder caused by the use of soft contact lenses. These cases demonstrated persistent corneal epithelial abnormalities, indolent ulceration, superficial stromal scarring, peripheral vascularization, and decreased visual acuity (worse than 20/400). Both cases were refractory to medical management, including discontinuation of contact lenses and topical medications. Autologous conjunctival transplantation restored the ocular surface with the return of good visual acuity (better than 20/40). Tissue culture demonstrated a decreased replication rate in the limbal epithelial cells, which suggests that epithelial stem cell dysfunction may be responsible for this ocular surface disease.

Salt-split human skin substrate for the immunofluorescent screening of serum from patients with cicatricial pemphigoid and a new method of immunoprecipitation with IgA antibodies.

In patients with cicatricial pemphigoid, immunoglobulins (usually IgG) and complement are deposited within the dermoepidermal junction and are detected by direct immunofluorescent staining of perilesional mucous membrane and/or skin with fluorescein-labeled antibodies to human immunoglobulins. Although rare, some patients also have circulating low-titer, anti-basement membrane zone autoantibodies. In this study, we report 11 patients with the clinical, histologic, and immunologic criteria for cicatricial pemphigoid who had circulating anti-BMZ autoantibodies as demonstrated by positive indirect staining of a normal human skin that had been fractured through the dermoepidermal junction by prolonged incubation in a cold, 1 mol/L sodium chloride solution. On this salt-split human skin substrate, 9 of the 11 patients (82%) had autoantibodies that bound to the epidermal roof, one serum stained only the dermal floor, and one serum stained both sides of the separation. The predominant class of immunoglobulin in the patients' sera that bound to the substrate was IgA; IgA was the single immunoglobulin in 55% and was associated with IgG in 18%. IgG was the only immunoglobulin detected in 27% of the cases. No specific protein was detected by either Western immunoblot or a new IgA immunoprecipitation procedure.

Endocapsular hypopyon: a clinical sign of localized endophthalmitis.

Chronic intraocular infection following cataract extraction and intraocular lens (IOL) implantation has been documented by several authors. We report a case of chronic, bacterial endophthalmitis that clinically correlates with previous pathologic studies in which the focus of infection was sequestered in the capsular sac between the IOL and the posterior lens capsule. Successful management did not require IOL removal.

A double-blind, placebo-controlled trial of acitretin for the treatment of psoriasis.

Acitretin, the active metabolite of etretinate, has the clinical advantage of a much shorter terminal elimination half-life. We report the results of a double-blind, placebo-controlled trial of acitretin (Soriatane) in 15 patients with moderate to severe psoriasis. Patients received 25 mg or 50 mg daily of acitretin or placebo in a double-blind fashion for 8 weeks and then were given 25 to 75 mg acitretin daily during an open study. Only two placebo patients completed the double-blind phase; one patient's psoriasis worsened, and one showed no significant change. All 15 patients then completed at least 8 weeks with 25 to 75 mg acitretin daily, with a moderate change in erythema, scaling, and induration (mean 28% to 37% improvement) but with minimal change in the percentage of body surface area involved. Prolonged treatment (greater than or equal to 20 weeks) with acitretin resulted in further significant improvement and a 44% reduction of involved surface area from baseline.

Corneal complications of herpes zoster ophthalmicus. Prevention and treatment.

Corneal complications of herpes zoster ophthalmicus include pseudodendritic keratitis, late mucous adherent keratopathy, varied forms of stromal keratitis, and exposure/neurotrophic keratopathy. Prophylactic therapy of acute herpes zoster ophthalmicus with oral acyclovir is of proven benefit in reducing the incidence of early pseudodendritic keratopathy and stromal keratitis but has no evident effect on exposure/neurotrophic keratopathy. Although early pseudodendritic keratitis is due to virus infection of epithelial cells, it is self-limited and does not require topical antiviral therapy. Stromal keratitis and associated epithelial mucous adherent keratopathy are responsive to topical corticosteroids but chronic therapy is often required and may prolong the duration of keratitis and result in cataract or secondary glaucoma. Exposure and neurotrophic keratopathy may respond to topical lubricants and correction of lid abnormalities but severely affected corneas may require tarsorrhaphy or conjunctival flap to maintain corneal integrity.

Acanthamoeba keratitis. A growing problem in soft and hard contact lens wearers.

Eleven contact lens-wearing patients presented with Acanthamoeba keratitis. Eight cases were culture- and/or stain-positive for Acanthamoeba and three were presumed to have Acanthamoeba keratitis based on history and clinical findings. Six wore daily wear soft contact lenses, two wore extended-wear soft contact lenses, one wore a polymethylmethacrylate hard contact lens, one wore a gas-permeable hard contact lens, and one wore a Saturn lens (combined hard and soft lens). Four patients used distilled water and salt tablet saline, three used tap water and salt tablet saline, two used tap water rinse, two used well water rinse or storage, and one used intravenous (IV) saline. It is apparent that all contact lens wearers are at some risk for Acanthamoeba keratitis developing if proper contact lens care is not maintained. Of great concern is the inability of most current chemical sterilization methods to kill the organism if the lens becomes contaminated. Heat disinfection will kill Acanthamoeba trophozoites and cysts but the lens must not be placed into contaminated solutions afterward. Prevention is very important because medical and surgical treatment failures are frequent. Eye care practitioners who fit contact lenses are advised to use heat disinfection for low-water content stock soft contact lenses, and to use hydrogen peroxide without a catalyst for a minimum of 6 hours for all other stock lens fitting sets, to specifically inquire about contact lens care habits used by their patients, and to discourage the use of homemade saline solutions.

Penetration of new azole compounds into the eye and efficacy in experimental Candida endophthalmitis.

We studied the penetration of three azole compounds, ketoconazole, itraconazole, and fluconazole, into the ocular tissues and fluids of rabbits in the presence and absence of ocular inflammation. Drug concentrations were compared with those found in serum and cerebrospinal fluid. The rank order of penetration into eye tissue was fluconazole greater than ketoconazole greater than itraconazole. Fluconazole penetrated freely into both inflamed and uninflamed eyes. The presence of inflammation improved penetration of all three compounds into ocular fluids and tissues. Penetration of these azoles into the anterior chamber of uninflamed eyes and into the cerebrospinal fluid was similar. All three azole compounds reduced the number of yeasts found in the eye in hematogenous Candida albicans endophthalmitis in rabbits when therapy was initiated within 24 h of inoculation. However, only ketoconazole significantly reduced yeast counts in the eye when therapy was postponed for 7 days.

Oral acyclovir in the treatment of acute herpes zoster ophthalmicus.

Seventy-one nonimmunocompromised patients with herpes zoster ophthalmicus, presenting within seven days of onset of characteristic skin eruption, were enrolled in a prospective, longitudinal, randomized, double-masked, placebo-controlled trial with oral acyclovir. In a previous interim report we noted more prompt resolution of dermatomal signs and symptoms with acyclovir treatment. There was also a reduction of viral shedding in acyclovir-treated patients coupled with a trend to greater rate of microdissemination of the virus in placebo-treated patients (Cobo LM, et al. Ophthalmology 1985; 92:1574-83). While further substantiating these findings, we report that a ten-day course of treatment with oral acyclovir (600 mg, five times a day) is well-tolerated and significantly reduces the incidence and severity of the most common complications of herpes zoster ophthalmicus: dendritiform keratopathy, stromal keratitis, and uveitis. While this acyclovir treatment regimen reduces the zoster-related pain during the acute phase of the disease, especially in patients treated within 72 hours of onset of skin lesions, it has no evident effect on either incidence, severity, or duration of post-herpetic neuralgia in the patients studied.

Early experience in extracapsular cataract surgery by residents.

We studied retrospectively the problems encountered by residents learning extracapsular cataract surgery and the variables influencing visual outcomes and complications in 130 patients. Although visual results were comparable to reported series by experienced surgeons, rates of complications were higher with 9% vitreous loss and 17% posterior capsule rupture in the first 25 cases of the average resident's experience. A learning curve depicting when complications occur shows that learning to avoid vitreous loss is a much faster process than learning to avoid posterior capsule rupture. Inter-resident variability in prevalence of complications was large. The axis of postoperative astigmatism was not consistent in residents at this stage of experience. Residents are not accurate judges of the effect faculty attendings have on visual outcomes and complication rates.

Oral acyclovir in the therapy of acute herpes zoster ophthalmicus. An interim report.

A prospective, randomized, double-masked, placebo-controlled clinical trial was conducted to study the effects of oral acyclovir on 55 patients with acute herpes zoster ophthalmicus. Treatment with oral acyclovir resulted in more prompt resolution of signs and symptoms, particularly in patients treated within 72 hours after onset of skin rash (P less than 0.05), and shortened the duration of viral shedding (P = 0.02). Vesicular skin lesions involving other dermatomes (microdissemination) occurred in five (19%) placebo-treated patients but in no acyclovir-treated patients (P = 0.03). Interim analysis of this longitudinal study suggests that the incidence and severity of secondary ocular inflammatory disease was reduced by acyclovir. Prolonged observation of these patients is ongoing to determine if oral acyclovir reduces post-herpes zoster neuralgia or the late ocular complications of ophthalmic zoster.

Endothelial cell repopulation after intracameral acetic acid irrigation.

A significant, but transient corneal edema followed inadvertent intracameral irrigation of acetic acid in two patients. Since postsurgical corneal edema generally indicates corneal endothelial dysfunction, the effects of acetic acid on corneal endothelium were studied in the cat where the endothelial regenerative capacity is thought to be comparable to that of humans. The anterior chambers of feline eyes were irrigated with 0.25% acetic acid or balanced salt solution in a double-masked manner. Marked corneal opacification and thickening were evident following exposure to the acetic acid but did not occur following irrigation with balanced salt solution alone. Following intracameral acetic acid irrigation, a few endothelial cells were found in the anterior chamber angle but could not be found on Descemet's membrane. Over an 8-week period gradual repopulation of Descemet's membrane by endothelial cells occurred, first in the periphery and later in the central cornea, coincident with resolution of corneal edema.

Early corneal findings in Cogan's syndrome.

We evaluated the ocular manifestations of Cogan's syndrome in 13 consecutive patients. The most frequent and earliest ocular finding was bilateral peripheral subepithelial keratitis consisting of faint, nummular lesions. The subepithelial keratitis was responsive to topical administration of corticosteroids. Peripheral subepithelial keratitis was seen in four patients and strongly suspected on review of history in three additional patients. Deep stromal keratitis was seen in two patients, while only one patient developed classic findings of Cogan's syndrome, ie. interstitial keratitis with vascularization. Additionally, five patients presented with noncorneal ocular inflammatory disease and deafness (atypical Cogan's syndrome). Early subepithelial keratitis in Cogan's syndrome may be mistakenly diagnosed as trival ocular inflammatory disease, and suppressed by topical corticosteroids, resulting in delayed diagnosis of Cogan's syndrome in the absence of classic corneal findings. Early diagnosis of Cogan's syndrome is important inasmuch as prompt treatment of cochlear symptoms with systemic corticosteroids may prevent or ameliorate deafness.