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Biomedical subjects

S Baltatzis

Publications and source records attributed to S Baltatzis.

At least 19 recordsLinked to original sources

Amniotic membrane inlay and overlay grafting for corneal epithelial defects and stromal ulcers.

OBJECTIVES: To determine the effect of amniotic membrane transplantation (AMT) on persistent corneal epithelial defects (PEDs) and to compare the efficacy between inlay and overlay techniques. METHODS: Thirty patients (30 eyes) underwent AMT for PED. The use of AMT was restricted to patients in whom all previous measures, including bandage contact lens and tarsorrhaphy, had failed. The amniotic membrane was placed on the surface of the cornea in overlay (group A) or inlay (group B) fashion. RESULTS: The PED healed after the first AMT in 21 eyes (70%) within an average of 25.5 days after surgery and recurred in 6 eyes (29%). Among the 22 eyes treated with an overlay AMT (group A), the PED healed after the first AMT in 14 eyes (64%) within an average of 24.5 days and recurred in 4 eyes (29%). Among the 8 eyes treated with an inlay AMT (group B), the PED healed within an average of 27.4 days after AMT, which did not statistically significantly differ from group A (P = .72). The PED healed after the first AMT in 7 eyes (88%) and recurred in 2 (29%) of 7 eyes. CONCLUSIONS: The AMT can be helpful in the treatment of PED in which all other conventional management has failed. However, the success rate in our study was not as high as that previously reported, and our results showed a high incidence of recurrences of epithelial defects. We did not find any difference between overlay and inlay techniques in terms of healing time and recurrence rate.

Adult↗

Ocular features associated with anticardiolipin antibodies: a descriptive study.

PURPOSE: To evaluate ocular features in patients presenting with inflammation in the presence of anticardiolipin antibodies. METHODS: A descriptive study of 13 patients presenting with idiopathic ocular inflammation involving anterior and posterior segment was performed. Patients were followed for a mean follow-up of 22 months (range, 1 to 125). A comprehensive report of ocular involvement, including visual symptoms, visual acuity, clinical characteristics, funduscopic and fluorangiographic features, was reported. Systemic associated symptoms were analyzed. Laboratory investigations included anticardiolipin antibody titers and isotypes, presence of other autoantibodies, and markers of immune system activation. RESULTS: The most common ocular symptom at presentation was blurred vision (eight patients) followed by redness and pain(three patients) and visual loss(two patients). Anterior segment abnormalities, including iritis (eight patients) scleritis (two patients) and filamentary keratitis (one patient), were present in 76% of patients, whereas the most represented feature of posterior involvement was retinal vasculitis (60%) followed by vitritis (38%), retinal detachment (15%), posterior scleritis (7%), and central retinal artery occlusion (7%). All patients had abnormal titers of anticardiolipin antibodies, predominantly IgG isotype; six had markers of immune system activation. CONCLUSIONS: Although posterior pole disease is more commonly associated with anticardiolipin antibodies, the anterior segment can also be involved with a wide spectrum of features. Scleritis has never been previously described as associated with anticardiolipin antibodies. Systemic symptoms are frequently present in association with ocular disease.

Adolescent↗

Epstein-Barr virus dacryoadenitis resulting in keratoconjunctivitis sicca in a child.

PURPOSE: To describe a case of severe dry eye syndrome in a child. METHODS: Observational case report. The authors describe a 10-year-old male with severe dry eyes who was profoundly disabled by pain and photophobia despite aggressive conventional therapy. Lacrimal gland histology was consistent with the primary Sjögren syndrome, and serologic and immunohistologic evidence supported the hypothesis of Epstein-Barr virus causality. RESULTS: Treatment with systemic acyclovir and cyclosporin A resulted in dramatic and rapid reversal of the profound sicca syndrome and enabled the patient to resume his normal activities. CONCLUSION: Epstein-Barr virus dacryoadenitis should be considered in the differential diagnosis of keratoconjunctivitis sicca in children. Epstein-Barr virus can cause keratoconjunctivitis sicca, which can be treated successfully with acyclovir therapy in addition to suppression of the inflammatory response.

Acyclovir↗

Chronic cicatrizing conjunctivitis in a patient with ocular cicatricial pemphigoid and fatal Wegener granulomatosis.

PURPOSE: To describe a case of chronic cicatrizing conjunctivitis in a patient with ocular cicatricial pemphigoid and Wegener granulomatosis. METHODS: Observational case report. A retrospective study. RESULTS: An 80-year-old man presented with chronic cicatrizing conjunctivitis, peripheral corneal thinning, and Wegener granulomatosis, which were diagnosed by his referring physician based on clinical (recurrent epistaxis, sinus congestion) and histopathologic features of nasal mucosa (granulomatous inflammation, vasculitis). A conjunctival biopsy performed by us disclosed features of active Wegener granulomatosis and ocular cicatricial pemphigoid, which indicate lack of control of both diseases with methotrexate treatment. The patient died of pulmonary complications from Wegener granulomatosis 1 week after our evaluation. CONCLUSION: Ocular cicatricial pemphigoid and Wegener granulomatosis are both potentially fatal autoimmune diseases. Ocular involvement in Wegener granulomatosis indicates poor control of the underlying systemic condition and is a marker for active vasculitis, which indicates the need for treatment with cyclophosphamide.

Aged↗

Methotrexate therapy for chronic noninfectious uveitis: analysis of a case series of 160 patients.

PURPOSE: To evaluate the outcomes of patients with chronic noninfectious uveitis unresponsive to conventional antiinflammatory therapy who were treated with methotrexate. DESIGN: Retrospective noncomparative interventional case series. PARTICIPANTS: All patients with chronic noninfectious uveitis treated with methotrexate at a single institution from 1985 to 1999. METHODS: Charts of patients seen on the Ocular Immunology & Uveitis Service at the Massachusetts Eye & Ear Infirmary were reviewed. Patients with chronic uveitis of noninfectious origin treated with methotrexate were included in the study. MAIN OUTCOME MEASURES: Control of inflammation, steroid-sparing effect, visual acuity, adverse reactions. RESULTS: A total of 160 patients met the inclusion criteria. Control of inflammation was achieved in 76.2% of patients. Steroid-sparing effect was achieved in 56% of patients. Visual acuity was maintained or improved in 90% of patients. Side effects requiring discontinuation of medication occurred in 18% of patients. Potentially serious adverse reactions occurred in only 8.1% of patients. There was neither long-term morbidity nor mortality caused by methotrexate. CONCLUSIONS: Methotrexate is effective in the treatment of chronic noninfectious uveitis that fails to respond to conventional steroid treatment. It is an effective steroid-sparing immunomodulator, is a safe medication, and is well tolerated.

Adolescent↗

Surgical excision of iris nodules in the management of sarcoid uveitis.

PURPOSE: To illustrate the role of surgical removal of iris nodules (granulomas) in the management of sarcoid uveitis. STUDY DESIGN: Two interventional case reports. METHODS: The authors describe the clinical course of two 10-year-old males with long-standing granulomatous uveitis refractory to medical antiinflammatory and immunomodulatory therapy. Both patients were seen with iris masses, which were excised and biopsied, with findings of sarcoidosis. MAIN OUTCOME MEASURES: Control of ocular inflammation as evidenced by decrease in inflammatory cells in both anterior and posterior chambers. RESULTS: On excision of the iris masses, the ocular inflammation was controlled in both patients. CONCLUSIONS: The authors hypothesize that iris granulomas may not only be products of persistent antigenic stimulation characteristic of sarcoidosis but subsequently become foci of continued cytokine production and ocular inflammation. Total surgical removal of the iris masses may help in the diagnosis and control of sarcoid uveitis refractory to medical management.

Child↗

Topical versus sub-Tenon's anesthesia without sedation in cataract surgery.

PURPOSE: To compare pain control using topical anesthesia with that using sub-Tenon's anesthesia for clear corneal phacoemulsification cataract surgery and foldable intraocular lens (IOL) implantation. SETTING: Departments of Ophthalmology, General Hospital Asklepeion Voulas and General Hospital of Athens, University of Athens, Athens, Greece. METHODS: One hundred consecutive patients scheduled for bilateral cataract surgery 1 to 2 months apart were prospectively randomized to receive topical anesthesia (100 eyes) or sub-Tenon's anesthesia (100 eyes). The randomization was stratified so that one half of first-eye surgeries and one half of second-eye surgeries were assigned to each anesthesia group, with each patient receiving each type of anesthesia once. All patients had clear corneal phacoemulsification with foldable IOL implantation. Patients were asked to rate their pain level on a 10-point scale for 4 periods: during the administration of the anesthetic agent, during surgery, immediately after surgery, and 24 hours postoperatively. The surgeon recorded his subjective assessment of ease of surgery and surgical complications using a standardized template. RESULTS: Eighty-one percent of patients who received topical anesthesia and 8% of patients who received sub-Tenon's anesthesia reported no pain during delivery of the anesthetic agent. The mean pain score was 0.19 +/- 0.39 (SD) in the topical group and 1.35 +/- 0.63 in the sub-Tenon's group. The difference between groups was statistically significant (P <.001). Seventy-two percent of patients in the topical anesthesia group and 86% in the sub-Tenon's anesthesia group reported no pain or slight discomfort during surgery (mean score 1.13 +/- 1.57 and 0.57 +/- 1.28, respectively) (P <.001). Ninety percent of topical anesthesia patients and 100% of sub-Tenon's anesthesia patients reported no pain or slight discomfort 30 minutes postoperatively (mean score 0.80 +/- 0.93 and 0.12 +/- 036, respectively) (P <.001). All patients in the topical anesthesia group and 77% in the sub-Tenon's group reported no pain 24 hours postoperatively (mean pain 0.00 +/- 0.00 and 0.23 +/- 0.40, respectively) (P <.001). Complications including prolonged akinesia of the globe, chemosis, and conjunctival hemorrhage occurred significantly more frequently in the sub-Tenon's than in the topical group (P <.001). CONCLUSIONS: Patients having cataract surgery under topical anesthesia had more intraoperative and postoperative discomfort than patients receiving sub-Tenon's anesthesia. However, patients having topical anesthesia reported less pain during its administration and had fewer complications. Both anesthesia methods provided high levels of pain control without additional sedation.

Aged↗

Pars plana vitrectomy in patients with intermediate uveitis.

OBJECTIVE: To describe the effect of pars plana vitrectomy in patients with intermediate uveitis. METHODS: Retrospective analysis of the clinical course and visual outcome following pars plana vitrectomy in patients with intermediate uveitis. RESULTS: Thirty-two patients (43 eyes) were included in the study. Pars plana vitrectomy was combined with cataract surgery in 22 of 43 eyes. The intermediate uveitis was associated with sarcoidosis in 16 eyes and multiple sclerosis in five eyes, and was idiopathic in 22 eyes. The mean (+/-SD) follow-up was 45.6 (+/-38) months (range: 6-146 months). In 19 of 43 eyes (44.1%), there was improvement in the course of uveitis, allowing the discontinuation of immunosuppressive treatment in seven patients. Cystoid macular edema resolved in 12 of 37 eyes (32.4%). Forty of 43 eyes achieved a better or retained their initial visual acuity. The remaining three eyes deteriorated by two or more lines in the Snellen chart due to the progression of cataract, chronic cystoid macular edema, and glaucomatous optic atrophy, respectively. CONCLUSIONS: The results of this study suggest that pars plana vitrectomy may have a beneficial effect on the course of uveitis and the associated complications of cystoid macular edema, thereby reducing the need for long-term immunosuppression. Pars plana vitrectomy combined with simultaneous cataract surgery can improve the visual outcome in these patients.

Adolescent↗

Long-term immunosuppressive treatment of serpiginous choroiditis.

OBJECTIVE: To determine the efficacy of immunosuppressive treatment in serpiginous choroiditis. DESIGN: The clinical courses were reviewed of six consecutive patients (12 eyes) with vision-threatening, steroid-dependent/resistant serpiginous choroiditis treated with a combination of immunosuppressive agents including azathioprine, cyclosporine, and cyclophosphamide. All patients underwent treatment for at least 12 months. RESULTS: The follow-up period ranged from 17 to 105 months (mean 57, median 43). All patients were able to taper oral steroids. Five patients discontinued all immunosuppressive medications after a treatment period of 12 to 69 months (mean 39 months). Immunosuppressive treatment was continued in one patient at a "low" maintenance dose. Ten eyes had improved visual acuities, while vision remained impaired in two due to macular scars. Recurrence was noted in two patients when an attempt was made to decrease the dose of immunosuppressive medication. Two patients experienced side effects which were reversed by decreasing the dose of the medications. CONCLUSION: Long-term immunosuppressive treatment appears to prolong remission and preserve vision in patients with serpiginous choroiditis.

Adult↗

A case of atypical Cogan's syndrome with uncommon corneal findings.

PURPOSE: We report a case of atypical bilateral interstitial keratitis associated with Cogan's syndrome. METHODS: A 28-year-old man presented with a 2-year history of recurrent bilateral keratitis. Bilateral hearing loss preceded the ocular symptoms by 2 years. The patient also complained of skin nodules, headache, back pain, and arthritis. Corneal finding were consistent with superior stromal keratitis with stromal neovascularization and lipid deposition in the stroma. The patient's audiogram revealed cochlear pathology compatible with Cogan's syndrome (sensorineural deafness). RESULTS: The patient was treated with topical steroids but eventually required corneal transplantation in the right eye as a consequence of progressive loss of vision secondary to progressive lipid keratopathy. Visual acuity at the patient's most recent follow-up evaluation was 20/40. CONCLUSION: This case represents an unusual type of interstitial keratitis associated with Cogan's disease. The absence of ocular symptoms at the time of initial ear involvement and the atypical presentation of the keratitis were responsible for the delay in diagnosis in this patient, resulting in hearing impairment.

Adult↗

Wegener's granulomatosis: the relationship between ocular and systemic disease.

OBJECTIVE: Wegener's granulomatosis (WG) is an etiologically obscure entity with multiple systemic manifestations. Ocular involvement is present in up to 58% of patients with WG. We describe a series of patients with ocular manifestations of WG to evaluate the presence of ocular lesions in the setting of systemic WG and to determine the value of ocular inflammation in the diagnosis of WG. METHODS: A computerized database was used to generate a list of patients cared for in the Ocular Immunology Service of the Massachusetts Eye and Ear Infirmary during the 10 year period 1988-98 with a diagnosis of Wegener's granulomatosis. A detailed chart review was undertaken to determine demographic characteristics, history, initial manifestation of WG, initial ocular presentation, biopsy results, laboratory testing results, treatment, total followup period, and final outcome. RESULTS: Forty-seven patients diagnosed with WG were identified. Twenty-eight were women (59.6%), 19 were men (40.4%). The average age was 53 years (range 18-90). Patients were divided into 4 groups. Group I included 27 patients (57.4%) who had systemic disease first and who subsequently developed an ocular lesion. Group II included 3 patients (6.3%) who had ocular inflammation first and who then subsequently developed systemic manifestations of WG. Group III included 3 patients (6.3%) who presented due to ocular symptoms but, on initial evaluation by us, were found to have occult systemic manifestations consistent with WG or biopsy evidence of WG. Group IV included 14 patients (30%) with ocular lesions and no history or presence of systemic disease at their last followup visit. CONCLUSION: Ocular inflammation can occur with or without obvious systemic manifestations of WG. It may represent the first sign of WG that enables the knowledgeable physician to diagnose this potentially lethal disease.

Adolescent↗

Effect of Fas and Fas ligand deficiency in resistance of C57BL/6 mice to HSV-1 keratitis and chorioretinitis.

PURPOSE: To investigate the effect of Fas and Fas ligand (FasL) deficiency on the development of herpes stromal keratitis and on the von Szily model of herpes retinitis in C57BL/6 mice, which are ordinarily resistant to development of both of these herpetic diseases. METHODS: Anterior chamber inoculation of the right eye of each mouse with various titers of HSV-1 (KOS strain) was performed. Both eyes of each mouse were enucleated on postinoculation day 15 and processed for histopathologic examination. HSV-1 was inoculated into one cornea of other mice, and the severity of stromal keratitis was scored. RESULTS: Contralateral destructive chorioretinitis developed in susceptible Balb/cByj mice (19/23); ipsilateral chorioretinitis did not occur (0/23). Stromal keratitis developed in susceptible C.AL-20 mice (15/16). None of the C57BL/6 (0/10 for keratitis or 0/20 for retinitis) developed inflammation. Neither did B6.SMN.C3H.gld (FasL deficient; 0/12 or 0/28) or B6.MRL.lpr (Fas deficient; 0/11 or 0/34) mice (keratitis or contralateral chorioretinitis). Minimal scattering of inflammatory cells in the contralateral retina but not destructive chorioretinitis was observed in two C57BL/6, three B6.SMN.C3H.gld, and five B6.MRL.lpr mice. Few inflammatory cells were also found in the ipsilateral vitreous and vitreoretinal interface (but not destructive chorioretinitis) of all C57BL/6, two gld, and three lpr mice. CONCLUSIONS: Immune dysregulation secondary to deficiency in Fas or FasL system does not influence the resistance of the C57BL/6 mice to develop herpes simplex keratitis or destructive herpes simplex chorioretinitis.

Animals↗

Gas-permeable scleral contact lens therapy in ocular surface disease.

PURPOSE: To describe the therapeutic benefits of nonfenestrated gas-permeable scleral contact lenses in the management of patients with ocular surface disease. METHODS: The charts of 49 consecutive patients (76 eyes) with ocular surface disease whose management included the use of gas-permeable scleral contact lenses were reviewed. We also developed a questionnaire to assess the impact of lens wear on subjective aspects of activities of daily living. RESULTS: The mean age of the 49 patients was 44.6 years (range, 3 to 87 years); 31 patients were female and 18 were male. The most common indication for fitting of the lenses was Stevens-Johnson syndrome (54 [71%] of the 76 eyes). Other indications included ocular cicatricial pemphigoid, exposure keratitis, toxic epidermal necrolysis, postherpetic keratitis, congenital deficiency of meibomian glands, superior limbal keratoconjunctivitis, Sjögren syndrome, and inflammatory corneal degeneration. The mean follow-up was 33.6 months (range, 2 to 144 months). Improvement in best-corrected visual acuity (defined as a gain of 2 or more Snellen lines) was observed in 40 (53%) of the eyes. In eight (53%) of the 15 eyes with active corneal epithelial defects at the time of lens fitting, the defects healed, whereas in the remaining seven eyes the corneal epithelial defects remained unchanged. Forty-five (92%) of the 49 patients reported improvement in their quality of life as a result of reduction of photophobia and discomfort. The mean wearing time of the gas-permeable scleral contact lenses was 13.7 hours per day (range, 4 to 18 hours). Many patients had preparatory surgical procedures before lens fitting (for example, punctal occlusion or mucous membrane grafting), and some had visual rehabilitation surgical procedures (for example, keratoplasty and/or cataract surgery) after lens fitting. CONCLUSIONS: Gas-permeable scleral contact lens wear provides an additional effective strategy in the surface management and visual rehabilitation of patients with severe ocular surface disease.

Adolescent↗

Secondary glaucoma in patients with juvenile rheumatoid arthritis-associated iridocyclitis.

PURPOSE: The prevalence and management of glaucoma were evaluated in patients with juvenile rheumatoid arthritis (JRA)-associated iridocyclitis. METHODS: The records of 69 patients with JRA-associated iridocyclitis were reviewed. RESULTS: Twenty-nine (42%) of these patients had secondary glaucoma or ocular hypertension. Glaucoma was controlled with topical treatment in only 7 of the 41 affected eyes (17%); systemic carbonic anhydrase inhibitor therapy resulted in control of another 8 eyes. Surgery controlled all but one of the remainder. CONCLUSION: Glaucoma is a common complication of JRA-associated iridocyclitis. It results from prolonged, inadequately treated intraocular inflammation and in some instances, from steroid use. Medical and surgical therapy for the glaucoma associated with JRA-uveitis is challenging and incompletely effective. We suspect that a more aggressive approach to the treatment of JRA-associated uveitis, earlier in the course of the disease may reduce this vision robbing contribution to the process.

Adolescent↗

Intraocular lens removal from [corrected] patients with uveitis.

PURPOSE: To report a series of patients with uveitis and cataract who had undergone cataract extraction with posterior chamber intraocular lens implantation and who subsequently had the intraocular lens removed because of progressive intraocular damage from inflammation. METHODS: Review of the records of 19 patients after removal of a posterior chamber intraocular lens. The decision to perform surgery was based on standard criteria after evaluation at a single uveitis referral center. RESULTS: The complications leading to intraocular lens removal were perilental membrane (eight eyes), chronic low-grade inflammation not responding to anti-inflammatory treatment (eight eyes), and cyclitic membrane resulting in hypotony and maculopathy (three eyes). After intraocular lens removal the inflammation subsided and the visual acuity improved or stabilized in 14 of the 19 eyes. The causes of further reduction in the visual acuity of the other five patients were macular edema (two patients), maculopathy resulting from hypotony (one patient), retinal detachment (one patient), and vitreous hemorrhage (one patient). CONCLUSIONS: Intraocular lens implantation can form part of a reasonable plan for visual rehabilitation of patients with uveitic cataract, but inclusion of an intraocular lens in the plan is not always in the overall long-term best interest of the patient. Intraocular lens removal may salvage useful vision for patients who continue to exhibit complications secondary to uveitis after cataract extraction and intraocular lens implantation, provided the intraocular lens is removed before irreparable damage has been done to macula or optic nerve.

Acute Disease↗

Management of uveitic glaucoma with Ahmed glaucoma valve implantation.

OBJECTIVE: To evaluate the safety and efficacy of Ahmed glaucoma valve implantation for the management of glaucoma associated with chronic uveitis. DESIGN: Retrospective, noncomparative case series. PARTICIPANTS: Nineteen patients (21 eyes) with chronic uveitis underwent Ahmed glaucoma valve implantation for uncontrolled glaucoma between 1995 and 1998. INTERVENTION: All patients had their uveitis controlled before surgery via immunomodulatory therapy. Ahmed glaucoma valve implantation was performed. Immunosuppression was continued in the early postoperative period for strict control of inflammation. MAIN OUTCOME MEASURES: Control of intraocular pressure (IOP). A secondary outcome measure was the number of antiglaucoma medications required to achieve the desired IOP. Visual acuity and complications associated with the surgery were monitored. RESULTS: The postoperative follow-up averaged 24.5 months. At the most recent visit, all 21 eyes had IOPs between 5 and 18 mmHg. The average pressure reduction after Ahmed glaucoma valve implantation was 23.7 mmHg. The average number of antiglaucoma medicines required to achieve the desired IOP was reduced from 3.5 before surgery to 0.6 after surgery. No eye lost even a single line of Snellen acuity at the most recent postoperative visit. Two eyes developed hypotony in the course of follow-up. One resolved without specific intervention, and the other eye required two autologous blood injections and tube ligature to correct the hypotony. One eye underwent Ahmed glaucoma valve replacement for abrupt valve failure. Two eyes underwent penetrating keratoplasty for reasons believed to be unrelated to the glaucoma surgery. Kaplan-Meier life-table analysis showed a cumulative probability of success after Ahmed glaucoma valve implantation of 94% at 1 year. CONCLUSIONS: Ahmed glaucoma valve implantation can be an effective and safe method in the management of uveitic glaucoma. The authors hypothesize that control of the patients' uveitis, through preoperative and long-term postoperative immunomodulatory therapy, may have contributed to the success rate reported herein.

Adolescent↗

Cytokine mRNA in BALB/c mouse corneas infected with herpes simplex virus.

PURPOSE: To investigate cytokine mRNA expression and the influence of acyclovir and tetrandrine on that expression in the corneas of mice infected with herpes simplex virus type 1 (HSV-1). METHODS: Male BALB/c mice were infected in the right cornea with HSV-1. The corneas were harvested from control normal mice and from untreated, acyclovir-treated and tetrandrine-treated mice 14 days after infection. The infected corneas of each group were divided into inflamed and uninflamed depending on clinical observation. After total mRNA extraction from the corneas, gene expression of interleukin 1 beta (IL-1 beta), IL-6, tumour necrosis factor alpha (TNF-alpha) and transforming growth factor (beta (TGF-beta) was analysed by reverse transcription polymerase chain reaction. RESULTS: No mRNA expression of the cytokines was found in normal corneas. IL-1 beta and TNF-alpha mRNA was seen in inflamed corneas, while mRNA expression of IL-6 and relatively weaker TGF-beta mRNA expression were found both in inflamed corneas and in infected but uninflamed corneas treated with acyclovir. TNF-alpha mRNA was present in the uninflamed corneas of tetrandrine-treated mice. No influence of either agent was found on TGF-beta gene expression. CONCLUSIONS: The results suggest that local IL-1 beta and TNF-alpha gene expression is required for corneal inflammation, whereas IL-6 and TGF-beta may exert antiviral and inflammation regulatory activities in HSV corneal infection.

Acyclovir↗