Viral Keratitis, Surgical Intervention in Viral Keratitis, Challenges in Diagnosis and Treatment of Viral Keratitis, HSV, HZV.

Viral keratitis is a significant cause of ocular morbidity and visual impairment worldwide. In recent years, there has been a growing understanding of the pathogenesis, clinical manifestations, and diagnostic modalities for viral keratitis. The most common viral pathogens associated with this condition are adenovirus, herpes simplex (HSV), and varicella-zoster virus (VZV). However, emerging viruses such as cytomegalovirus (CMV), Epstein-Barr virus (EBV), and Vaccinia virus can also cause keratitis. Non-surgical interventions are the mainstay of treatment for viral keratitis. Antiviral agents such as Acyclovir, Ganciclovir, and trifluridine have effectively reduced viral replication and improved clinical outcomes. Additionally, adjunctive measures such as lubrication, corticosteroids, and immunomodulatory agents have alleviated symptoms by reducing inflammation and facilitating tissue repair. Despite these conservative approaches, some cases of viral keratitis may progress to severe forms, leading to corneal scarring, thinning, or perforation. In such instances, surgical intervention becomes necessary to restore corneal integrity and visual function. This review article aims to provide an overview of the current perspectives and surgical interventions in managing viral keratitis. The choice of surgical technique depends on the extent and severity of corneal involvement. As highlighted in this article, on-going research and advancements in surgical interventions hold promise for further improving outcomes in patients with viral keratitis.

Initial High-Dose Prophylaxis and Extended Taper for Mushroom Keratoplasty in Vascularized Herpetic Scars.

PURPOSE: To report the outcomes of initial high-dose and extended taper of antiviral and steroid prophylaxis for the treatment of eyes with high-risk vascularized herpetic corneal scars that underwent 2-piece mushroom keratoplasty (MK). DESIGN: Prospective interventional case series. METHODS: In this single-center study, 52 consecutive eyes with vascularized (≥2 quadrants) herpetic corneal scars underwent 2-piece microkeratome-assisted MK. Initial high-dose and extended taper of combined oral and topical antiviral and steroid prophylaxis was administered. Outcome measures were best spectacle-corrected visual acuity (BSCVA), refractive astigmatism (RA), endothelial cell density, immunologic rejection, herpetic recurrence, and graft failure rates. RESULTS: Excluding patients with vision-impairing comorbidities, baseline BSCVA (1.73 ± 0.67 logMAR) significantly improved annually during the first 2 years (P < .001, P = .016), reaching 0.17 ± 0.18 logMAR at year 2, and remaining stable up to 10 years (P = .662). At 2 years, 86% of eyes saw ≥20/40, 55% saw ≥20/25, and 18% saw ≥20/20 Snellen BSCVA. RA exceeded 4.5 diopters in 7% of cases after wound revision for high-degree astigmatism in 7 cases. Endothelial cell loss was 40.9% at 1 year with an annual decline of 3.1% over 10 years. The 10-year cumulative risk for immunologic rejection, herpetic recurrence, and graft failure was 9.7%, 7.8%, and 7.6%, respectively. CONCLUSIONS: Initial high dose and extended taper of antiviral and steroid prophylaxis for MK in high-risk, vascularized herpetic corneal scars achieves clinical outcomes that remain stable for up to 10 years after surgery with minimal risk of immunologic rejection, herpetic recurrence and graft failure.

Conjunctival Epithelial Ingrowth After Penetrating Keratoplasty.

PURPOSE: To report a case of conjunctival epithelial ingrowth after penetrating keratoplasty. METHODS: A 57-year-old woman with herpetic corneal keratitis, endotheliitis, and bullous keratopathy underwent penetrating keratoplasty (PKP) and secondary cataract surgery. One month after cataract surgery, an epithelial ingrowth was observed at the 5 o'clock donor host junction. Ingrowth extended into the anterior chamber and along the iris surface by 9 months. Another PKP was performed, and the excised graft was submitted for histopathology. RESULTS: The graft showed CK13-positive and CK3-negative cells lining the endothelial surface, indicating the conjunctival origin of ingrown epithelium. Ten months postoperatively, no recurrence of ingrowth was observed. CONCLUSIONS: We experienced a rare case of conjunctival epithelial ingrowth after penetrating keratoplasty. There was no recurrence of the ingrowth after surgical removal, and the conjunctival origin may explain the relatively benign course of the complication.

Descemet Membrane Endothelial Keratoplasty in Irreversible Corneal Edema Due to Herpes Simplex Virus Endotheliitis.

PURPOSE: To report the clinical outcome and postoperative course of Descemet membrane endothelial keratoplasty (DMEK) in irreversible corneal edema due to herpes simplex virus (HSV) endotheliitis. METHODS: This is a retrospective, noncomparative, interventional case series. Nineteen eyes of 19 patients underwent standard DMEK combined with cataract surgery (triple DMEK) between May 2016 and April 2018. All patients received perioperative oral acyclovir (ACV) and prednisolone. Patients were followed up on day 1, on day 7, at 1 month, and then at 3 monthly intervals. Preoperative and postoperative best spectacle-corrected visual acuity (BSCVA), graft clarity, pachymetry, and endothelial cell loss after 1 year were recorded. Postoperative complications and HSV recurrence were noted until the last follow-up visit. RESULTS: All eyes were phakic with variable grades of cataract with a preoperative BSCVA of 1.0 logarithm of the minimum angle of resolution or worse. The mean follow-up period was 19.3 ± 5.4 months. After 1 year, 14 (73.7%) eyes achieved a BSCVA of 0.3 or better. Seventeen (89.5%) patients had a clear graft at the last visit without any rejection episode. One graft failed after 16 months. After 3 months, the mean pachymetry reduced from 667.1 ± 62.1 to 512.8 ± 27.1 µm (P < 0.001). The mean endothelial cell loss after 1 year was 36.7 ± 13.4%. Three (15.8%) eyes had recurrence: one with recurrent endotheliitis and 2 with dendritic keratitis despite oral ACV, which responded to oral valacyclovir and ACV eye ointment. One patient had re-recurrence of endotheliitis after 20 months. CONCLUSIONS: DMEK in persistent corneal edema after HSV endotheliitis remains challenging but has encouraging outcomes. The postoperative course may be complicated by HSV recurrence. Prophylactic oral antivirals for 1 year or more and topical antivirals are useful for the prevention of recurrence.

The characteristics of Posner-Schlossman syndrome: A comparison in the surgical outcome between cytomegalovirus-positive and cytomegalovirus-negative patients.

This retrospective observational study aims to report the clinical characteristics and surgical results in eyes with Posner-Schlossman syndrome (PSS), and compare these outcomes between cytomegalovirus (CMV)-positive and -negative eyes.We reviewed the medical records of 21 consecutive immunocompetent patients clinically diagnosed with PSS between the years 2010 and 2018. Aqueous humor was collected from all the affected eyes to detect if CMV was present, and polymerase chain reaction (PCR) was performed using the herpesvirus family primers.The average period between the initial PSS attack and aqueous humor sampling at our institute was 9.3 years. Out of the 21 patients, 62% were CMV-positive. Regardless of CMV status, the mean intraocular pressure (IOP), mean deviation (MD), and central corneal endothelium cell (CEC) density, at the initial examination at our institute were already significantly worse in the affected eyes than in the unaffected eyes (all P values < .05). The average visual acuity (VA) was only significantly worse in the CMV-positive group (P = .02). Out of all the patients, those that were CMV-positive had undergone more glaucoma surgeries (P = .056). Fourteen patients underwent either a trabeculectomy (TRAB) or a trabeculotomy (LOT), and their IOP significantly reduced following surgery (P < .001). In 85.7% of those that had surgery, their IOP was successfully lowered to less than 20 mm Hg.Long-lasting PSS causes a decrease in VA, MD, and the CEC density. A prompt diagnosis is required, and an appropriate treatment plan should be formulated. In those patients with PSS that develop uncontrolled glaucoma, both TRAB and LOT may be effective in controlling IOP.

Long-term outcomes of penetrating keratoplasty for corneal complications of herpes zoster ophthalmicus.

BACKGROUND/AIM: To review the long-term outcomes of penetrating keratoplasty (PKP) for corneal complications of herpes zoster ophthalmicus (HZO). METHODS: We reviewed the medical records of 53 eyes of 53 patients who underwent PKP due to corneal complications of HZO at the Kellogg Eye Center. RESULTS: The mean age of patients at the time of PKP was 68.0±16.4 years, with a follow-up of 4.0±3.8 years and quiescent period of 6.5±5.3 years from active HZO to PKP. Preoperatively, 25 (47.2%) eyes were completely anaesthetic, while 16 (30.2%) had deep corneal neovascularisation in four quadrants. Comorbid ocular disease, including cataract, glaucoma and macular disease, was present in 25 (47.2%) eyes. Twenty patients (37.8%) received acyclovir for the entire postoperative period. There were no recurrences of zoster keratitis in any eye. The most common complications were difficulty healing the ocular surface (12/53, 22.6%) and glaucoma (14/53, 26.4%). Thirty per cent of the eyes required one or more additional postoperative procedures, most commonly tarsorrhaphy (10/53, 18.9%) and amniotic membrane graft (6/53, 11.3%). At 1, 2-4 and ≥5 years, 94%, 82% and 70% grafts remained clear, respectively. Visual acuity improved at 1 year postoperatively (p<0.0001), but this improvement was not sustained. There was no significant benefit of long-term acyclovir on visual acuity (p=0.2132) or graft survival (p=0.241). CONCLUSIONS: Even in eyes with significant preoperative risk factors, PKP for the corneal complications of HZO can achieve favourable tectonic and visual results. Although most grafts remained clear, long-term visual potential may be limited by comorbid ocular diseases. Prophylactic postoperative oral acyclovir did not improve outcomes.

Surgical management of herpetic keratitis.

PURPOSE OF REVIEW: The purpose of this review is to discuss the options for, and recent developments in, the surgical treatment of herpes keratitis. Although the mainstay of treatment of herpetic keratitis is topical or oral antiviral agents, surgical intervention may be necessary for corneal melting or long-term complications such as scarring, lipid keratopathy, necrotizing keratitis, and neurotrophic keratitis. RECENT FINDINGS: There are a number of surgical therapies available for herpes keratitis. Preferred therapeutic modalities differ based on the size, causation, and location of the infection but consist of either replacement of the infected tissue or structural support of the tissue to allow healing. Incremental improvements in the existing treatment modalities have made them more effective, easier, and safer, whereas novel therapies such as corneal neurotization are starting to be described in ophthalmic literature. SUMMARY: Several options are available for surgically managing the complications of herpes keratitis. Ophthalmologists should select the optimal procedure based on the individual patient's situation. VIDEO ABSTRACT: http://links.lww.com/COOP/A28.

Descemet membrane endothelial keratoplasty for corneal decompensation caused by herpes simplex virus endotheliitis.

We report a case of corneal decompensation caused by recurrent herpetic endotheliitis that was treated successfully with Descemet membrane endothelial keratoplasty (DMEK). A 62-year-old woman presented with a history of recurrent herpetic infections in the right cornea. After topical and systemic treatment with antivirals and steroids for 5 months, DMEK combined with cataract surgery was performed. Two weeks after DMEK, the corrected distance visual acuity (CDVA) in the affected eye was 0.3 (20/60). One year postoperatively, the CDVA was 1.0 (20/20) and the slitlamp biomicroscopy showed no signs of graft rejection or herpetic recurrence. Corneal decompensation caused by herpetic endotheliitis used to be treated exclusively with penetrating keratoplasty. Descemet membrane endothelial keratoplasty combined with cataract surgery seems to be a favorable surgical option in the treatment of corneal endothelial decompensation after recurrent herpetic endotheliitis.

Rate of Retinal Detachment after Early Prophylactic Vitrectomy for Acute Retinal Necrosis.

PURPOSE: To compare the rate of retinal detachment after acute retinal necrosis in eyes that underwent early vitrectomy versus no early vitrectomy. METHODS: Charts of patients (61 eyes) who presented to Texas Retina Associates between January 1, 2006 and December 30, 2014 for acute retinal necrosis were reviewed. Charts with incomplete documentation or follow-up less than 6 months were excluded. Twenty-nine remaining eyes were divided into two groups: early vitrectomy and no early vitrectomy. Primary outcome measure was rate of retinal detachment. RESULTS: Out of 29 eyes, 12 underwent early vitrectomy within 30 days of diagnosis and 17 either underwent vitrectomy after 30 days or did not undergo prophylactic vitrectomy at all. Three out of 12 eyes (25%) developed retinal detachment in the early vitrectomy group versus 10 out of 17 eyes (59%) in the no early vitrectomy group (p = 0.076). CONCLUSIONS: Early vitrectomy within 30 days may prevent retinal detachment after acute retinal necrosis.

Long-term outcomes of the Boston type I keratoprosthesis in eyes with previous herpes simplex virus keratitis.

PURPOSE: To report the long-term outcomes of the Boston type I keratoprosthesis (Kpro) in eyes with prior herpes simplex virus (HSV) keratitis. METHODS: Retrospective review of all Kpro procedures performed by a single surgeon from 1 May 2004 to 1 January 2015. RESULTS: 13 of 173 Kpro procedures were performed in 11 eyes with prior HSV keratitis. There was not a significant difference in the percentage of eyes with and without prior HSV keratitis with preoperative (9% vs 8%, p=1.00) or postoperative (57% vs 60%, p=1.00) corrected distance visual acuity (CDVA) ≥20/200 or in the percentage of contralateral eyes with preoperative CDVA ≥20/50 (55% vs 30%, p=0.18). While several postoperative complications occurred approximately twice as often in eyes with prior HSV keratitis, including persistent epithelial defect (63.6% vs 34.1%; p=0.10), corneal infiltrate (27.3% vs 12.3%; p=0.17) and sterile vitritis (18.2% vs 9.4%; p=0.31), only cystoid macular oedema (45.5% vs 12.3%; p=0.01) was significantly more common. Similarly, while the Kpro retention failure rate in eyes with prior HSV keratitis was twice than that in eyes without it (0.15 vs 0.07 per year), the difference was not statistically significant (p=0.09). CONCLUSION: As greater than half of patients with unilateral HSV keratitis undergoing Kpro implantation have CDVA ≥20/50 in the contralateral eye, and as the Kpro retention failure rate in eyes with prior HSV keratitis is twice than that in eyes without prior HSV keratitis, caution should be exercised when considering Kpro implantation in these patients.

Changes in Higher-Order Aberrations After Phototherapeutic Keratectomy for Subepithelial Corneal Infiltrates After Epidemic Keratoconjunctivitis.

PURPOSE: To investigate how corneal aberrations change after phototherapeutic keratectomy (PTK) for subepithelial infiltrates after adenoviral keratoconjunctivitis. METHODS: The records of patients who underwent transepithelial PTK for subepithelial infiltrates were retrospectively reviewed. Preoperative best-corrected visual acuity (VA) and the results of slit-lamp biomicroscopy examinations were recorded. The PTK procedure was performed under topical anesthesia with an Amaris excimer laser. Patients' manifest refraction values, topographical examination results, and corneal aberrations before and after surgery were analyzed. RESULTS: Twenty-four eyes of 16 women (84.3%) and 3 men (15.7%) were treated. The mean follow-up time was 6.0 ± 2.5 (range: 3-12) months, and the mean ablation depth was 82.3 ± 1.0 (range: 80-88) µm. Postoperative median best-corrected VA increased from 0.6 (range: 0.4-1.0) logarithm of the minimum angle of resolution to 0.2 (range: 0.1-0.5) logarithm of the minimum angle of resolution (P = 0.048), coma decreased from 0.56 (range: 0.29-0.37) to 0.44 (range: 0.07-0.74), secondary astigmatism decreased from 0.45 (range: 0.12-1.9) to 0.17 (range: 0.03-0.49), and total higher-order aberrations decreased from 1.24 (range: 0.61-6.74) to 0.9 (range: 0.33-1.64) (P = 0.008, 0.0032, and 0.018, respectively). CONCLUSIONS: PTK is an effective method for treating corneal opacity after epidemic keratoconjunctivitis, which yields significant improvements in both VA and visual quality.

Reactivation of Herpes Zoster Keratitis With Corneal Perforation After Zoster Vaccination.

PURPOSE: We present a case of reactivated herpes zoster keratouveitis of 6 years duration with corneal perforation requiring penetrating keratoplasty shortly after inoculation with herpes zoster vaccine (Zostavax, Merck, Quebec, Canada). METHODS: Retrospective case report. RESULTS: A 67-year-old woman with a 5-year history of recurrent unilateral herpes zoster keratouveitis in her right eye presented with another recurrence 2 weeks after Zostavax vaccination. Three months later, she developed descemetocele and 2 months afterward, corneal perforation, which was managed by penetrating keratoplasty. Immunohistopathological examination disclosed positive staining for varicella zoster virus in most of the keratocytes adjacent to the descemetocele and perforation, most vividly in the deeper two-thirds of the stroma where the keratocytes were most dense, but not in corneal epithelium or endothelium. Electron microscopic examination showed universally severely degenerated corneal keratocytes in the corneal stroma adjacent to the perforation with variable numbers of herpes virus capsids present in half of these cells. Only a rare normal-appearing keratocyte was identified in the more peripheral corneal stroma. CONCLUSIONS: We present a case of reactivation of herpes keratouveitis shortly after vaccination with Zostavax in a patient with previous herpes zoster ophthalmicus. We demonstrate, for the first time, ultrastructural evidence consistent with inactive virus capsids in diffusely degenerated keratocytes in the extracted corneal tissue.

Descemet Stripping Automated Endothelial Keratoplasty Outcomes in Patients With Cytomegalovirus Endotheliitis.

PURPOSE: There is currently limited information regarding the outcomes of endothelial keratoplasty in eyes with cytomegalovirus (CMV) endotheliitis. We report the results of Descemet stripping automated endothelial keratoplasty (DSAEK) for endothelial failure secondary to CMV. METHODS: This is a retrospective review of 4 eyes of 4 patients with CMV endotheliitis and DSAEK. CMV was confirmed in each case by a positive aqueous tap on qualitative polymerase chain reaction. The clinical characteristics of the patients and postoperative outcomes were studied. RESULTS: The mean age of the 4 patients was 69.6 ± 8.1 years. Two were ethnically Vietnamese, 1 Chinese, and 1 Lebanese. All were immunocompetent. Three eyes had presented with hypertensive uveitis and 1 with bullous keratopathy. Twelve DSAEKs were performed in total in the 4 eyes. Five grafts were performed without any perioperative treatment with oral valganciclovir. All subsequently failed after a mean of 8.0 ± 3.8 months. Seven grafts were managed with oral valganciclovir; 2 of these grafts failed after 18 and 37 months, and 1 graft had primary graft failure. Four grafts are currently surviving, despite an episode of CMV reactivation in 2 grafts. CONCLUSIONS: In cases of unexplained corneal decompensation or early graft failure after uncomplicated DSAEK, a diagnosis of CMV infection must be considered. Subsequent management of DSAEK in such cases remains challenging. The postoperative course can be complicated by CMV reactivation, which may masquerade either as graft rejection or graft failure. Long-term treatment with oral valganciclovir or topical ganciclovir may be required to decrease graft failure rates.

Case report: a diagnostically challenging conjunctival mass caused by the Epstein-Barr virus.

We present a paediatric case of infectious mononucleosis in a 13-year old, manifesting with follicular conjunctivitis and a conjunctival mass in one eye with no evidence of leucocytosis on the blood count. The diagnosis was confirmed following surgical excision and biopsy. The case represented a diagnostic challenge due to its atypism and given the steady increase in the prevalence of EBV-related ocular diseases in the last years, this report can serve as an example to prompt earlier serological tests to identify the aetiology in similar cases. This is important because EBV can be treated with acyclovir early in the active viral phase.

Amniotic Membrane Transplantation for the Treatment of Infectious Ulcerative Keratitis Before Elective Penetrating Keratoplasty.

PURPOSE: Emergency keratoplasties for inflamed eyes are considered to have a worse prognosis because of immunologic graft rejection. Amniotic membranes have antiinflammatory and antiangiogenic abilities. Therefore, amniotic membrane transplantation (AMT) was performed to stabilize the situation of eyes with severe infectious keratitis before elective penetrating keratoplasty (PK). METHODS: Retrospective, nonrandomized observational case series. Seven to 41 days (median, 20 days) after the onset of intensive antiinfectious medication, an AMT (6 multigrafts and 6 sandwich) was performed in 12 patients [8 men and 4 women; age 46-80 years (median, 66 years)] with herpetic (n = 5), bacterial keratitis (n = 3), or combinations (n = 4). Three to 12 months (median, 5 months) after cessation of the inflammatory status of the eye, a central elective PK (diameter, 7-8 mm) became feasible in 10 eyes. Follow-up ranged from 4 to 38 months (median, 20 months) after PK. RESULTS: The primary success rate of AMT was 11/12 (92%). Five recurrences (41%) were treated successfully 4 times by repeat AMT (sandwich) and 1 time by emergency PK. In 2 of the 12 eyes, an irreversible endothelial immunologic graft reaction appeared 18 and 21 months after PK. One eye suffered from reversible recurrence of herpetic keratitis on the corneal graft. At the end of the follow-up, 10 of 12 grafts (83%) were clear. CONCLUSIONS: A rapid decrease in the inflammatory reaction and a fast reepithelialization because of AMT after intensive antiinfectious medication in case of severe ulcerative keratitis may help to avoid an emergency keratoplasty and improves the prognosis of the elective keratoplasty.

Long-term results of keratoplasty in patients with herpes zoster ophthalmicus.

PURPOSE: To report the long-term results of keratoplasty in patients with herpes zoster ophthalmicus (HZO). METHODS: All 14 patients underwent keratoplasty for a corneal scar or a perforated corneal ulcer due to HZO at the Wills Eye Institute from January 1999 to August 2011. RESULTS: We performed 9 penetrating keratoplasties and 1 deep anterior lamellar keratoplasty for corneal scarring, and 4 tectonic penetrating keratoplasties for perforated corneal ulceration due to HZO. Eight of the 14 eyes had a temporary tarsorrhaphy concurrent with graft. Postoperative follow-up time ranged from 12 to 132 months (mean 64 ± 38). Postoperatively, the most common complications were dense superficial punctate keratopathy and severe dry eye because of neuropathic keratopathy in 8 eyes, graft rejection in 5 eyes, and secondary glaucoma in 4 eyes. All grafts were clear, and best spectacle-corrected visual acuity was 20/40 or better in 6 eyes (42.8%) and 20/100 or better in 9 eyes at their final evaluation (64.2%). CONCLUSIONS: Although the sample size is small, we demonstrate that very good visual results in long-term follow-up can be achieved when keratoplasty is performed in patients with herpes zoster virus keratopathy. We believe that longer quiescent waiting period between active herpes zoster ocular involvement and keratoplasty may promote better visual results.