Anti-glaucoma agents-induced pseudodendritic keratitis presumed to be herpetic simplex keratitis: a clinical case series.

Anti-glaucoma agents-induced corneal toxicity may be misdiagnosed as herpetic simplex keratitis (HSK). In our study, nineteen glaucoma patients were presumed to have HSK before referral. Corneal lesions were classified into (I) linear pseudodendritic lesions formed by elevated opacified cells, (II) linear pseudodendritic lesions formed by grouped superficial punctate keratitis (SPK), (III) satellite full-thickness epithelial defects, (IV) satellite lesions formed by elevated opacified cells, and (V) geographic lesions formed by grouped SPK. We observed thirty-one events, with 15 in the lower and 16 in the central corneas. There were 21 (67.7%) type II, five (16.1%) type V, two (6.5%) of each for types III and IV, and one (3.2%) type I events. Among linear lesions (types I and II), 17 (77.3%) had horizontal and 5 (22.7%) had curvilinear orientations. Exposure duration to the last-added anti-glaucoma agent was three days to 14.5 years. About half of the events (16/31, 51.6%) used prostaglandin analogues, and 30/31 (96.8%) applied benzalkonium chloride (BAK)-containing agents. All lesions resolved within two months after decreasing offending medications or enhancing protection of ocular surface. In conclusion, anti-glaucoma agents-induced pseudodendritic keratitis presents majorly in central-lower cornea as horizontally linear lesions, and BAK-containing agents are observed in the most events.

Topical tacrolimus ointment for treatment of refractory anterior segment inflammatory disorders.

PURPOSE: To report 4 cases of patients treated with topical tacrolimus ointment 0.03% for ocular inflammatory conditions refractory to traditional treatment. METHODS: Four patients were treated topically with tacrolimus 0.03% ointment twice daily: 2 patients with blepharokeratoconjunctivitis, 1 patient with severe atopic keratoconjunctivitis, and 1 patient with chronic follicular conjunctivitis. RESULTS: Three patients had a dramatic improvement of their ocular condition as early as 2 weeks after starting tacrolimus ointment. One patient developed a herpes simplex virus dendrite after 1 week of tacrolimus use. CONCLUSION: Tacrolimus ointment appears to be an effective alternative for certain ocular inflammatory conditions refractory to traditional treatments. There may be an increased risk of herpes simplex virus keratitis associated with topical use. Our results support previous literature of patients benefiting from topical tacrolimus use.

Dendritic keratopathy associated with beta-blocker eyedrops.

Four patients with chronic open-angle glaucoma developed a dendriform corneal epithelial lesion. Two were associated with the use of topical betaxolol for 2 months and 6 weeks, and two were related to topical levobunolol. Resolution occurred within 2 weeks of discontinuation of the beta-blocker eyedrop. The distinctive pattern of dendritic epithelial keratopathy associated with these topical medications may be due to epithelial toxicity with subsequent regeneration.

Recurrent HSV-1 corneal epithelial lesions induced by timolol iontophoresis in latently infected rabbits.

Herpes simplex virus type 1 (HSV-1) ocular shedding and recurrent corneal epithelial lesions were assessed following ocular iontophoresis of 0.01% timolol at 0.8 mAmp for 8 min for 3 consecutive days in 17 rabbits latently infected with HSV-1 strain McKrae. The collection of ocular tear film for the detection of HSV-1 ocular shedding and the slit lamp biomicroscopic evaluation for HSV-1 epithelial lesions began on day 4 after the first iontophoresis and continued for 7 consecutive days. The tear film was collected on a Dacron swab with care being taken to avoid swabbing the corneal epithelium. The observed HSV-1 lesions were characterized as deep punctate lesions, dendritic lesions and geographic epithelial defects. The ratio of total days of eyes exhibiting HSV-1 epithelial lesions to the total number of observation days was 113/235 (48%). There were 46 punctate lesions, 27 dendritic lesions and 40 geographic epithelial defects. The ratio of positive swabs to total swabs was 77/235 (33%). Of the 113 positive lesion days, 65 (58%) were associated with a positive swab. Of the 77 positive swabs, 65 (84%) were associated with an epithelial lesion. Of the 122 negative lesion days, 110 (90%) were associated with a negative swab. Of the 158 negative swabs, 110 (70%) were associated with no epithelial lesions. By chi-square analysis, there was a significant association between HSV-1 swabs and HSV-1 lesions (P less than 0.001). These results demonstrate that ocular iontophoresis of timolol induces both HSV-1 ocular shedding and recurrent HSV-1 corneal epithelial lesions in rabbits latently infected with HSV-1 strain McKraw.

[Experimental tyrosine keratopathy in rabbits]. / Experimentelle Tyrosinkeratopathie bei Kaninchen.

Tyrosine was given to White New Zealand and Chinchilla bastard rabbits. The corneal epithelium showed pinpoint lesions and a pseudokeratitis dendritica from the fourth day on. In spite of continued tyrosine dosage these lesions disappeared clinically within 6 days. Scanning electron microscopy revealed necrosis of isolated epithelial cells even after the twentieth day of tyrosine dosage. Specular microscopy sporadically revealed glittering pre-endothelial structures. It was found by light microscopy that there was a tendency to focal proliferation of corneal epithelial cells and a vacuolization in the basal epithelial cell layers. Endothelial defects may be responsible for circumscribed edema of the corneal stroma.

Sequelae of botulinum toxin injection.

A total of 136 injections was given to 83 patients for strabismus (99 injections), blepharospasm (29 injections), and spastic entropion (eight injections). All four patients with entropion experienced temporary benefits and early recurrence; one injection resulted in temporary paralytic ectropion. Two of 13 patients treated for blepharospasm developed transient bilateral blepharoptosis. Temporary and related sequelae of extraocular muscle injection included one periocular hemorrhage, one total ophthalmoplegia, and a 44% incidence (29 of 66 patients) of blepharoptosis, which in two patients lasted more than six months. Within three days of injection one patient developed homolateral acute herpes simplex keratitis and a second died of an acute myocardial infarction. No causal relationship for these events has been established.

Reactivation of murine latent HSV infection by epinephrine iontophoresis.

Iontophoresis of epinephrine into the cornea of previously infected mice was used in an attempt to induce reactivation of latent herpes simplex virus (HSV) infection of the trigeminal ganglia. BALB/c mice infected with HSV-1 strain McKrae following corneal scarification developed a latent infection of the trigeminal ganglia within 15 days. At 28 days postinfection, mice were subjected to a 3-day cycle of iontophoresis of epinephrine (0.01%) into the cornea. Ocular shedding of HSV occurred in 16/23 (70%) of stimulated mice; these animals did not shed HSV in the 3-day period prior to iontophoresis. Spontaneous shedding of HSV, however, was noted in 3/97 (3%) mice not subjected to epinephrine iontophoresis. "Infectious" virus was isolated only from the trigeminal ganglia of stimulated mice, whereas "latent" virus was isolated from the trigeminal ganglia of both stimulated and nonstimulated mice. All virus isolates were verified to be HSV by neutralization with a known HSV-1 antiserum. This ocular system thus allows for the study of the full spectrum of latent HSV infections, including latency, ganglionic reactivation, and peripheral virus shedding.

Dendritic corneal lesions associated with soft contact lens wear.

Two cases of dendritic lesions associated with soft contact lens wear occurred that were referred as cases of herpes simplex keratitis. Lesions resolved after temporary discontinuation of soft lens wear and conversion to thermal sterilization. The pseudodendrite is presumed to result from a toxic or hypersensitivity reaction to contact lens material or to components of chemical sterilization systems. Several dendritic lesions may be confused with herpes simplex. The soft contact lens associated pseudodendrite is added to this list. Accurate diagnosis can be made by careful attention to the clinical history and the morphologic features of the dendrite in most cases.

Experimental ulcerative herpetic keratitis. III. Evaluation of hyperimmune gammaglobulin therapy.

The value of hyperimmune gammaglobulin (HGG) therapy in ulcerative herpetic keratitis was assessed in rabbits. HGG treated of early disease in normal rabbits was very effective, producing a 10-fold rise in the virus concentration needed to infect 50% of sites (CID50) and an 88% inhibition of ulceration after 2 days. The efficacy of the gammaglobulin preparations tested depended on their anti-HSV antibody content. Established disease was considerably less responsive to HGG therapy. No conclusive effect of HGG therapy could be demonstrated in rabbits with a previous HSV skin infection ('immunised'). Corticosteroid-induced geographic ulceration in immunised rabbits was not prevented by concurrent HGG therapy. The findings indicate that HGG is unlikely to represent a useful therapy for ulcerative herpetic keratitis but that it may be valuable in primary disease and in long-term prophylaxis.

Experimental ulcerative herpetic keratitis. II. Influence of topical corticosteroid in immunised rabbits.

Since the great majority of patients possess immune response to herpes simplex virus (HSV), the influence of a topical anti-inflammatory corticosteroid (0.1% clobetasone butyrate) on ulcerative herpetic keratitis was studied in rabbits with a previous HSV skin infection (immunised) and compared with that in normal rabbits. Corticosteroid treatment had a much greater ulceration-exacerbating effect in immunised than in normal animals. On day 7 the mean area of ulceration in immunised rabbits were 3 times greater in treated eyes. 0.01% clobetasone butyrate treatment had less effect on immunised rabbits; 0.001% had no effect. It is concluded that the immunised rabbit provides a useful experimental model for studying the relationship between concentration of topical anti-inflammatory agents and enhancement of herpetic ulceration.