Arden H. Wander

Conjunctival Involvement in Paraneoplastic Pemphigus

Paraneoplastic pemphigus is a recently described autoimmune inflammatory mucocutaneous disease associated with an underlying neoplasm. Although histopathologic and direct immunofluorescence findings of involved skin and mucous membranes are consistent with pemphigus vulgaris, indirect immunofluorescence and immunoprecipitation study results are unique. We treated two patients with non-Hodgkins lymphoma and paraneoplastic pemphigus. Both patients had bilateral bulbar conjunctival hyperemia and diffuse papillary tarsal conjunctival reactions. One patient had sloughing of conjunctival epithelium and the other had tarsal conjunctival cicatrization and forniceal shortening. Histopathologic findings of conjunctivae obtained from both patients were consistent with pemphigus vulgaris. Diffuse deposition of IgG and C3 in the intercellular substance of the conjunctival epithelium was demonstrated by direct immunofluorescence. Indirect immunofluorescence testing disclosed binding of autoantibodies to rodent bladder and intestinal epithelium. Immunoprecipitation disclosed antibodies reactive to Desmoplakin I (250 kd), bullous pemphigoid (230 kd), Desmoplakin II (210 kd) and 190-kd proteins. Ophthalmologists and pathologists should be aware of the conjunctival changes in paraneoplastic pemphigus.

Ophthalmia Nodosa Caused by Tarantula Hairs

A young woman presented with ocular discomfort after handling her pet tarantula. Multiple fine hairs were detected on the eyelids, in the palpebral and bulbar conjunctiva, and in the corneal epithelium and stroma. In addition, foreign body granulomas were found in the conjunctiva. Six months later, peripheral chorioretinal lesions were seen. The clinical and histologic findings in this case closely resemble the findings in ophthalmia nodosa caused by caterpillar hairs.

Living Retinal Nematode (Filarial-Like) Destroyed with Photocoagulation

A motile worm creating tracks upon the pigment epithelium of the retina was observed in each of two patients. The fundus findings resembled pseudoretinitis pigmentosa. Unilateral macular degeneration resulted in one patient. The worm was a nematode, probably a filaria. This report represents the third and fourth intraocular filariae found in the United States. To our knowledge, it is the first report of living, intraretinal filarial-like worms destroyed by photocoagulation.

Extending the Duration of Tear Film Protection in Dry Eye Syndrome: Review and Retrospective Case Series Study of the Hydroxypropyl Cellulose Ophthalmic Insert

Options for extending the duration of tear film protection in dry eyes include artificial tear formulations with enhanced viscosity/polymeric systems, ocular ointments and gels, and, recently, the hydroxypropyl cellulose ophthalmic insert (Lacrisert(R); distributed by Aton Pharma, Inc., Lawrenceville, NJ, USA). The goal in using these agents is to achieve a balance between maximizing tear film stability and ocular surface retention, while simultaneously maintaining or improving vision, comfort, and convenience. In this article, various agents are reviewed, and findings are presented from a retrospective study of patients who used hydroxypropyl cellulose ophthalmic inserts within the previous 2 years. The median length of therapy with the insert was 5.3 years, and nearly 65% of patients had used it for more than 2 years. Findings suggest that the hydroxypropyl cellulose ophthalmic insert is a relatively safe, tolerable, and effective therapy for dry eye, either alone or in conjunction with other therapies.

APPEARANCE OF IMMUNE CELLS AND EXPRESSION OF MHC II DQ MOLECULE BY FIBROBLASTS IN ALKALI-BURNED CORNEAS

Corneal alkali burns are characterized by persistent inflammatory response and recurrent epithelial erosions. We examine whether immune cell types, i.e., T-cells and B-cells, play a role in this devastating process. Rabbit alkali-burned corneas that healed for 1—49 days were subjected to immunostaining with monoclonal antibodies (mAb) LI 1/135 (anti-T-cells), and 2C4 (anti-MHC II DQ). Serum was collected weekly and subjected to Western blot immunostaining to detect antibodies against denatured corneal proteins. Our observations demonstrated that all injured corneas reepithelialized within 3 days but then developed recurrent erosions. Immunohistochemical studies revealed that PMN, monocytes, and B-cells labeled by 2C4 mAb and T-cells labeled by LI 1/135 mAb appeared in the periphery of the cornea at 1 day after alkali burn. Many of these myeloid and lymphoid cells invaded the central stroma after 2 weeks of injuries when the alkali-burned corneas were heavily vascularized. In addition, some fibroblastic cells also expressed the MHC II DQ molecules in the alkali-burned corneas that had healed for <2 weeks. Plasma cells appeared in granulation tissue of injured corneas that had healed for <3 weeks. Western blot analysis demonstrated a production of heterogeneous antibodies in a majority of the rabbits (11 of 14) to various denatured corneal proteins (between 80 kDa and 25 kDa) at 5 weeks of alkali burn. Inflammatory cell types, i.e., PMN, macrophages could be found underneath the detached epithelium. These observations are consistent with the notion that the myeloid and lymphoid cells may participate in and complicate the healing of corneal alkali burns.

The pathogenesis of herpetic ocular disease in the guinea pig.

SummaryA detailed study of the pathogenesis of herpetic eye disease in the Guinea pig was undertaken to further develop this animal model. Several well-known HSV-1 strains were tested for their ability to produce disease and cause acute and latent infections of the trigeminal ganglion: McKrae, KOS, McIntyre, RE, and Shealey. Two HSV-2 strains failed to cause eye infections. The Shealey strain [HSV-1 (Sh)] produced the most severe eye infections, characterized by epithelial and stromal disease, corneal vascularization and ulcerative blepharitis. Consequently, HSV-1 (Sh) was selected as the prototype strain for this study. The frequency and severity of HSV-1 (Sh) eye disease patterns was determined by a semi-quantitative rating scale, which permitted accurate monitoring of the temporal development of the disease patterns cited above. Virus shedding from infected eyes was also quantified. All of the HSV-1 strains tested established trigeminal ganglionic latency with varying frequency, although HSV-1 (Sh) latency approached 100 percent. The kinetics of acute ganglionic infection by HSV-1 (Sh) was determined, and peak virus titers occurred on the third day after corneal inoculation. This study emphasizes the usefulness of the Guinea pig model for investigations on the pathogenesis, prevention and treatment of herpetic eye infections.

Long-term use of hydroxypropyl cellulose ophthalmic insert to relieve symptoms of dry eye in a contact lens wearer: case-based experience.

Objectives: To report a case in which hydroxypropyl cellulose ophthalmic inserts were successfully used for the treatment of dry eye disease in a contact lens (CLs) wearer for more than 25 years. Methods: Review of clinical findings in a female CL wearer with dry eye spanning more than 30 years. The patient was diagnosed with the Sjögren syndrome and demonstrated inadequate lacrimation as assessed by Schirmer testing. Slitlamp examination demonstrated bilateral corneal stippling with fluorescein and signs of superior limbic keratoconjunctivitis. Results: Initially, the patients symptoms improved with infrequent use of artificial tears. As the signs and symptoms of dry eye disease worsened, the patient initiated therapy with once-daily hydroxypropyl cellulose ophthalmic inserts. Punctal plugs and updating to increasingly oxygen-permeable soft CLs, in combination with continued use of the inserts, largely controlled the signs and symptoms of dry eye disease during a 25-year period. Simultaneous use of the hydroxypropyl cellulose ophthalmic inserts and CLs was well tolerated without any significant side effects or changes in visual acuity. Conclusions: Dry eye is a chronic disease often requiring long-term management. In this case, daily use of hydroxypropyl cellulose ophthalmic inserts effectively treated autoimmune dry eye, providing symptomatic relief, and resulted in improved objective measures of disease severity across several decades. Such an experience is consistent with the available evidence-based data for hydroxypropyl cellulose ophthalmic inserts and supports their use in clinical practice for the treatment of moderate-to-severe dry eye disease.

Herpes simplex and recurrent corneal disease.

The management of a patient with ocular HSV is a challenge for the ophthalmologist. Attacks may vary in clinical presentation with each episode. Patients should be instructed to contact their ophthalmologist at the first sign of a problem. Because a recurrent attack may be painless, patients may be reluctant to seek medical attention. Therefore, I give patients three easy warning signs to remember. They are instructed to contact me if the eye becomes red or painful or the vision decreases. Those patients with a history of ocular HSV who will undergo immuno-suppression (e.g., renal transplant) must be watched closely (Fig. 5). I often recommend several drops per day of prophylactic trifluridine for these patients while they are on steroid therapy and immunosuppressives. Because of the dangers of corticosteroids without antiviral cover, I instruct patients to emphasize their history of herpetic ocular disease to any physician who may want to treat the patient with corticosteroids. In those patients in whom a trigger mechanism can be identified, I may also recommend prophylactic antiviral agents to be taken at the time that such mechanisms are likely to be activated. Because minor trauma can precipitate a recurrent attack in some patients, I discourage cosmetic contact lens wear in these patients. There has been no form of therapy to date that has decreased the recurrence rate for HSV infections. Research to develop a vaccine that would prevent herpetic latency is ongoing. Such a vaccine theoretically would make herpetic ocular disease nonrecurrent . In our own laboratories at the University of Cincinnati College of Medicine, we have been working with a promising vaccine prepared against the early viral-induced proteins. Thus far, this vaccine has prevented latency in experimental animals. Perhaps it will prevent latency in the human. Further work with newer antiviral agents such as acyclovir may aid in our fight against this disease. Interferon may also find a place in the possible prevention and treatment of recurrent herpetic ocular disease. In the meantime, different forms of recurrence with almost every conceivable complication can occur. The ophthalmologist must, therefore, be diligent in the management of his or her patients with ocular herpetic disease.

Toxicity and Tolerance of 9-(2-Hydroxyethoxymethyl)Guanine

Acyclovir [9-(2-hydroxyethoxymethyl)guanine] is a new antiviral agent which has specific activity in virus-infected cells. The drug has a high therapeutic index in animal and laboratory models but had not been tested for toxicity in human eyes at the time of this study. A randomized double-blind study on patients requiring antiviral therapy for treatment or prophylaxis of herpetic ocular infections revealed minimal irritation associated with topical administration. Further controlled studies will be necessary to evaluate this compounds clinical efficacy.

Somatotopic distribution of corneal afferent neurons in the guinea pig trigeminal ganglion

The size and somatotopic distribution of corneal afferent neurons in the guinea pig trigeminal ganglion were determined using a retrograde axonal tracing technique. Wheat germ agglutinin-horseradish peroxidase (WGA-HRP) was applied to the central cornea of the guinea pig and the animals were perfusion-fixed 48 h later. In addition, a preliminary study examined corneal afferent neurons in two animals latently infected with the herpes simplex virus by corneal inoculation. The majority of WGA-HRP-labelled neurons were located in the ophthalmic division of the ipsilateral ganglion. A clear dorsoventral somatotopic arrangement of labelled corneal afferent neurons was noted. The size of the neurons averaged 23 microns and the number of cells per ganglion averaged 205. By contrast, the number of labelled neurons in latently infected ganglia averaged less than 50. No size or morphological distinctions could be made between neurons from uninfected or latently infected ganglia. The results of this study have provided for the first time the precise location and somata diameter of primary afferent corneal neurons within the guinea pig trigeminal ganglion.