Asim V. Farooq

Herpes Simplex Epithelial and Stromal Keratitis: An Epidemiologic Update

Herpes simplex virus (HSV) is associated with a variety of ocular diseases, including epithelial and stromal keratitis. HSV can cause stromal opacification and is believed to be the leading cause of infectious blindness in the developed world. An improved understanding of the global burden of HSV keratitis, including the incidence of severe vision loss, could have a significant effect on prevention and treatment and place it in perspective among causes of corneal ulceration. We found that the global incidence of HSV keratitis is roughly 1.5 million, including 40,000 new cases of severe monocular visual impairment or blindness each year. We also discuss relevant epidemiologic issues regarding HSV epithelial and stromal disease.

Mediators and Mechanisms of Herpes Simplex Virus Entry into Ocular Cells

The entry of herpes simplex virus into cells was once thought to be a general process. It is now understood that the virus is able to use multiple mechanisms for entry and spread, including the use of receptors and co-receptors that have been determined to be cell-type specific. This is certainly true for ocular cell types, which is important as the virus may use different mechanisms to gain access to multiple anatomic structures in close proximity, leading to various ocular diseases. There are some patterns that may be utilized by the virus in the eye and elsewhere, including surfing along filopodia in moving from cell to cell. There are common themes as well as intriguing differences in the entry mechanisms of herpes simplex virus into ocular cells. We discuss these issues in the context of conjunctivitis, keratitis, acute retinal necrosis, and other ocular diseases.

An investigative peptide-acyclovir combination to control herpes simplex virus type 1 ocular infection.

PURPOSE To investigate the efficacy of a combination treatment composed of the cationic, membrane-penetrating peptide G2, and acyclovir (ACV) in both in vitro and ex vivo models of herpes simplex virus 1 (HSV-1) ocular infection. METHODS The antiviral activity of a combined G2 peptide and ACV therapy (G2-ACV) was assessed in various treatment models. Viral entry, spread, and plaque assays were performed in vitro to assess the prophylactic efficacy of G2, G2-ACV, and ACV treatments. In the ex vivo model of HSV-1 infection, the level of viral inhibition was also compared among the three treatment groups via Western blot analysis and immunohistochemistry. The potential change in expression of the target receptor for G2 was also assessed using immunohistochemistry and RT-PCR. RESULTS Statistically significant effects against HSV-1 infection were seen in all treatment groups in the viral entry, spread, and plaque assays. The greatest effects against HSV-1 infection in vitro were seen in the G2-ACV group. In the ex vivo model, statistically significant anti-HSV-1 effects were also noted in all control groups. At 24 hours, the greatest inhibitory effect against HSV-1 infection was seen in the ACV group. At 48 hours, however, the G2-ACV-treated group demonstrated the greatest antiviral activity. Syndecan-1, a target of G2, was found to be upregulated at 12-hours postinfection. CONCLUSIONS This study shows that G2-ACV may be an effective antiviral against HSV-1 (KOS) strain when applied as single prophylactic applications with or without continuous doses postinfection.

Corneoscleral Laceration and Ocular Burns Caused by Electronic Cigarette Explosions.

Purpose: To report cases of acute globe rupture and bilateral corneal burns from electronic cigarette (EC) explosions. Methods: Case series. Results: We describe a series of patients with corneal injury caused by EC explosions. Both patients suffered bilateral corneal burns and decreased visual acuity, and one patient sustained a unilateral corneoscleral laceration with prolapsed iris tissue and hyphema. A review of the scientific literature revealed no prior reported cases of ocular injury secondary to EC explosions; however, multiple media and government agency articles describe fires and explosions involving ECs, including at least 4 with ocular injuries. Conclusions: Given these cases and the number of recent media reports, ECs pose a significant public health risk. Users should be warned regarding the possibility of severe injury, including sight-threatening ocular injuries ranging from corneal burns to full-thickness corneoscleral laceration.

The role of herpesviruses in ocular infections

Ocular infections caused by herpesviruses are an important cause of morbidity. The majority of cases are believed to be associated with herpes simplex virus type-1 (HSV-1), although HSV-2, varicella zoster virus (VZV), cytomegalovirus (CMV) and Epstein-Barr virus (EBV) are also associated with various ocular diseases. The ability of some herpes viruses to infect various anatomic regions of the eye may be facilitated by entry processes that are cell- type specific, and in many cases may occur more frequently in the immunocompromised. The elimination of the role of herpesviruses in ocular disease remains elusive, as they often develop life-long latency in a large proportion of humans. Experimental vaccines for ocular HSV have shown some benefit in animal models, a result that has not been adequately demonstrated in clinical trials. Meanwhile, ocular involvement in VZV remains unpredictable, and CMV retinitis continues to be an important cause of blindness in those infected by HIV.

Fungal Orbital Cellulitis: Presenting Features, Management and Outcomes at a Referral Center

Abstract Purpose: To report a series of patients with fungal orbital cellulitis who underwent exenteration surgery and describe presenting features, management and outcomes at a referral center. Methods: Retrospective case series. Results: From November 2011 to March 2014, four patients underwent orbital exenteration for fungal orbital cellulitis at the University of Illinois. Three patients had mucormycosis and one had aspergillosis. All patients were treated with intravenous antifungals and underwent orbital exenteration. Two patients were successfully treated with supplemental intra-orbital catheter delivery of amphotericin B. Presenting visual acuity in the affected eye ranged from 20/25 to no light perception. Some level of ophthalmoplegia was present in three patients. Significantly elevated intraocular pressure was found in two patients. All patients with mucormycosis were found to have uncontrolled diabetes mellitus. One patient had a history of myelodysplastic syndrome, chronic hepatitis C infection, polysubstance abuse and Crohn’s disease. Another patient had a history of alcoholic liver cirrhosis, Crohn’s disease treated with systemic immunosuppression and renal cell carcinoma. The patient with aspergillosis had myelodysplastic syndrome and portal hypertension, and the initial presentation resembled giant cell arteritis. Two of four patients died during their hospitalization. Conclusions: Fungal orbital cellulitis has a high mortality rate despite aggressive antifungal treatment and orbital exenteration performed soon after the diagnosis is confirmed. Patients often have a history of immunosuppression and the onset may be insidious. There must be a high rate of suspicion for fungal orbital cellulitis given the appropriate signs and medical history in order to avoid treatment delay.

Infections after refractive surgery.

Purpose of review The purpose of the review is to provide a summary of the recent literature concerning infections after refractive surgery pertinent to each procedure category. Recent findings New data from a large retrospective study suggest that the incidence of post-laser assisted in-situ keratomileusis infectious keratitis is declining. Additionally, recent case studies have reported viral, fungal, and Acanthamoeba pathogens. Corneal collagen cross-linking is emerging as an alternative therapeutic option for early stage post-LASIK infectious keratitis. Postoperative bandage contact lens used in patients undergoing surface ablation procedures may confer a higher risk of infection because of greater colonization rates in those individuals, such as healthcare providers, with relatively high risk of exposure to potential pathogens. In the setting of post-penetrating keratoplasty astigmatism, femtosecond laser astigmatic keratotomy procedures pose a risk of infectious keratitis and even endophthalmitis. Lastly, recent case reports of endophthalmitis after refractive lens procedures highlight the importance of postoperative monitoring for this sight threatening, albeit rare, complication. Summary The risks and management of infections after surgical refractive procedures vary widely depending on the specific technique employed. As technology and treatment options continue to evolve with further research, we anticipate continued success in the management of postoperative infections after refractive surgery.

Corneal Ectasia and Hydrops in Ocular Hypotony: The Corneal Crease.

Purpose: To report the association of chronic ocular hypotony with the development of progressive corneal ectasia and hydrops. Methods: Retrospective case series. Results: Three patients with ocular hypotony were referred for corneal evaluation and found to have ectasia and acute corneal hydrops in their hypotonous eye(s). Clinically, the globes were easily deformable with either external digital palpation and/or simple blinking. All 3 patients had a history of chronic iridocyclitis, including one with juvenile idiopathic arthritis. In each case, the area of thinning was narrow and arcuate in configuration, distinctive from other ectatic disorders. Also uncharacteristically, the acute hydrops resolved rapidly within 2 to 3 weeks without surgical intervention. In 1 case, severe thinning with perforation occurred requiring urgent penetrating keratoplasty. Conclusions: This case series demonstrates a unique clinical entity in which corneal ectasia and hydrops developed in the setting of ocular hypotony and easily deformable corneas, in a pattern unlike previously described forms of ectasia. Acute hydrops, even with associated corneal perforation, demonstrated a short and self-limited course. Corneal ectasia and irregular astigmatism should be suspected as a cause of unexplained visual loss in the ever-increasing number of patients with chronic, stable ocular hypotony. Further study is warranted to determine the pathophysiology of corneal ectasia in this setting, which may include mechanical and inflammatory factors.

Biofilm Formation on Bandage Contact Lenses Worn by Patients with the Boston Type 1 Keratoprosthesis: A Pilot Comparison Study of Prophylactic Topical Vancomycin 15 mg/mL and Linezolid 0.2%

Objectives: To determine the rate of biofilm formation on bandage contact lenses worn by patients with the Boston type 1 keratoprosthesis (K-Pro) while on prophylactic topical vancomycin versus linezolid. Methods: Patients wearing a bandage contact lens (BCL) with a K-Pro were eligible for enrollment. After irrigation of the ocular surface with 5% povidone-iodine solution, each patient was placed on either topical vancomycin 15 mg/mL or linezolid 0.2% BID for one month. At the one-month visit, the BCL was collected and stored in fixative solution. Standard photographs were taken of each lens at high magnification using scanning electron microscopy (SEM), which were subsequently analyzed for evidence of biofilm. Results: Nineteen contact lenses were obtained from 12 K-Pro patients at the Illinois Eye and Ear Infirmary. Zero of eight (0%; 95% CI=0 to 37%) contact lenses from patients treated with topical vancomycin, and 1 of 11 (9%; 95% CI=0 to 41%; P-value=1.00) contact lenses from patients treated with topical linezolid were found to have biofilm formation at one month as detected by SEM. None of the patients developed a clinically significant infection while on either prophylactic vancomycin or linezolid during the study period. Conclusions: Overall, the rate of biofilm formation as detected by SEM on the surface of bandage contact lenses was low. These results suggest that vancomycin and linezolid are both relatively effective in reducing biofilm-forming bacterial growth at one month. Accordingly, linezolid may be an effective alternative to vancomycin in patients with allergy or intolerance. However, further investigation is required to develop evidence-based antibiotic prophylaxis regimens.

Alternating Skew Deviation in Association with Anti-Glutamic Acid Decarboxylase Antibodies

ABSTRACT The presence of an elevated anti-glutamic acid decarboxylase (GAD) antibody level has been associated with a number of eye movement abnormalities as well as other findings, including cerebellar ataxia and insulin-dependent diabetes mellitus. Skew deviation in association with anti-GAD antibodies has not been previously reported. Here the authors report a case of alternating skew deviation along with cerebellar-brainstem signs in a patient with an elevated anti-GAD antibody titre. Follow-up neurologic evaluation after treatment with intravenous immunoglobulin revealed improvement in cerebellar-brainstem signs, whereas ophthalmic evaluation was stable.