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.

Decision-making in Herpes Simplex viral keratitis grafts.

Background: Keratoplasty after healed herpes simplex viral keratitis is a challenge due to problems arising preoperatively, intraoperatively, and postoperatively. Purpose: In this video, we describe the necessary challenges and the steps, which can be taken to prevent and manage those cases of healed herpes simplex virus (HSV) keratitis that would require a keratoplasty. Synopsis: The video talks about both the typical and atypical features of HSV keratitis, clinical examination, the scenarios which would require a keratoplasty, problems arising intraoperatively and how to manage them, and finally how to approach these high-risk grafts postoperatively. Highlights: Our video highlights the diagnosis of HSV keratitis, which cases are ready for surgery, and preoperative, intraoperative, and postoperative considerations before corneal transplantation in healed HSV keratitis. Decision-making before corneal transplant in HSV grafts can become more structured if these points are followed. Video Link: https://youtu.be/xMT7Ki8vuc4.

Evidence in the prevention of the recurrence of herpes simplex and herpes zoster keratitis after eye surgery.

OBJECTIVE: Herpetic keratitis, either due to herpes simplex keratitis (HSK) or herpes zoster ophthalmicus (HZO), can recur after eye surgery.º Prophylaxis is postulated as necessary to avoid it. The objective of this study was to review the scientific evidence on the preventive methods used in the perioperative period in patients previously affected by HSK/HZO. METHODS: An exhaustive search was carried out in the PubMed and Web of Science databases to identify relevant articles on prophylaxis and risk of recurrence of HSK/HZO in patients undergoing eye surgery up to 31 December 2019. RESULTS: There is strong evidence that oral prophylaxis should be recommended after penetrating keratoplasty in patients who have previously had HSK/HZO. For other types of surgery, the evidence is less compelling. However, a latent period of inactivity should be considered between disease and oral prophylaxis. CONCLUSIONS: Penetrating and lamellar keratoplasty, corneal crosslinking, cataract surgery, and photorefractive and phototherapeutic surgery cause an alteration of the subbasal nerve plexus of the cornea. Due to surgical trauma, as well as the modulation of the ocular immune response caused by steroids applied in the postoperative period, it is possible to induce the reactivation of HSK/HZO, which is common in some cases. Within this article, we discuss the available evidence for HSK/HZO prophylaxis in eye surgery. Further studies are necessary to define the real risk of HSK/HZO recurrence after ocular surgeries, particularly in cataract surgery, and to confirm the efficacy of perioperative prophylaxis with anti-HSK/HZO antivirals.

Outcome of Lamellar Graft Patching for the Treatment of Noninfectious Corneal Perforations.

PURPOSE: The aims of this study were to evaluate the clinical outcome of lamellar graft patching used for treating noninfectious corneal perforations and to determine the clinical factors affecting tectonic integrity. METHODS: This retrospective study includes a total of 71 eyes of 67 patients who underwent lamellar graft patching for the treatment of corneal perforations due to persistent epithelial defects secondary to limbal stem cell deficiency (LSCD, 21 eyes; 29.6%), peripheral ulcerative keratitis (17 eyes; 23.9%), neurotrophic keratitis due to herpes simplex keratitis (HSK, 14 eyes; 19.7%), and other causes (19 eyes; 26.8%). We evaluated the tectonic integrity of the globe, visual outcomes, and postoperative complications. RESULTS: Tectonic integrity was achieved in 53 eyes (74.6%). The survival proportions of eyes that achieved clear grafts were 77.8% and 65.2% at 12 and 24 months, respectively. Graft failure was observed in 19 eyes (26.8%). The survival rate of tectonic integrity and eyes that finally achieved a clear graft was significantly worse in eyes with LSCD compared with those without ( P < 0.001). The logarithm of minimal angle resolution improved significantly from 1.79 ± 0.98 to 1.22 ± 0.87 at 12 months and 1.08 ± 0.81 at 24 months. Postoperative complications included cataract formation (32 eyes, 45.1%), intraocular pressure rise (23 eyes, 32.4%), recurrent perforations (15 eyes, 21.1%), infectious keratitis (14 eyes, 19.7%), recurrence of herpes simplex keratitis (7 eyes, 9.9%), and traumatic graft dehiscence (1 eye, 1.4%). CONCLUSIONS: Lamellar graft patching is an effective and safe surgical treatment for noninfectious corneal perforations; however, careful attention to severe complications is necessary, especially in eyes with LSCD.

Ocular surgery after herpes simplex and herpes zoster keratitis.

PURPOSE: The recurrence of herpetic stromal keratitis (HSK) and herpes zoster ophthalmicus (HZO) has been reported after a variety of ocular surgeries. The aim of this study was to review the evidence on the preventive methods employed in the perioperative period in patients having undergone HSK/HZO. METHODS: The PubMed and Web of Science databases were the main resources used to conduct the medical literature search. An extensive search was performed to identify relevant articles concerning the prophylaxis against and risk of HSK/HZO recurrence in patients undergoing ocular surgery up to December 31, 2019. RESULTS: The disturbance of the corneal nerve plexus occurs during several ocular surgeries including penetrating keratoplasty, lamellar keratoplasty, corneal cross-linking, cataract surgery, as well as photorefractive and phototherapeutic procedures. Such trauma, as well as modulation of the ocular immunological response caused by steroids applied postoperatively, might engender the HSK/HZO reactivation which is not uncommon. There is strong evidence that oral prophylaxis should be recommended just after surgery in patients undergoing penetrating keratoplasty and having suffered from HSK/HZO. For other types of surgeries, the evidence is less compelling; nevertheless, a period of disease quiescence and oral prophylaxis should still be considered. CONCLUSIONS: Within the article, we discuss the available evidence for HSK/HZO prophylaxis in ocular surgery. Additional studies would be required to define the real risk of HSK/HZO recurrence following eye surgeries, and particularly cataract surgery, and to confirm the utility of perioperative HSK/HZO prophylaxis.

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.

Herpetic Corneal Keratopathy Management Using Ipsilateral Supratrochlear Nerve Transfer for Corneal Neurotization.

BACKGROUND: Neurotrophic keratopathy (NK) is a potentially sight-threatening condition caused by impairment in the trigeminal corneal innervations with decrease or loss of corneal sensitivity. This prospective study aimed to evaluate the outcomes of surgical neurotization of the cornea using ipsilateral supratrochlear nerve transfer in patients with herpes-induced NK. METHODS: An ophthalmologist and a plastic surgeon performed an interdisciplinary corneal neurotization in 13 eyes of 13 patients after preoperative exclusion of forehead sensation impairment. A 3-cm supra-eyebrow incision allowed for microsurgical supratrochlear nerve dissection, and a subconjunctival tunneling was performed for the nerve transfer. Neurotrophic keratopathy was assessed preoperatively and every 3 months postoperatively using slit-lamp microscopy, the corneal sensitivity test, specular microscopy, and in vivo confocal microscopy. RESULTS: The surgeries had no major complications. The average disease duration from cornea denervation to surgery was 15.2 years. The mean follow-up duration was 18.5 ± 6 months. The symptoms exhibited subjectively improved visual acuity, and objectively improved visual analog scale and NK grading. The subepithelial corneal nerve plexus was found at 9 months postoperatively. The corneal thickness decreased and the corneal endothelial count increased postoperatively. CONCLUSIONS: This is the largest series of corneal neurotization using direct ipsilateral supratrochlear nerve transfer. It is a minimally invasive method to restore corneal sensitivity and treat NK successfully within 1 year without a sural nerve graft. A long-term follow-up is needed for further assessment.

Short-term results of acellular porcine corneal stroma keratoplasty for herpes simplex keratitis.

BACKGROUND: Corneal transplantation is a common surgical intervention for restoring vision loss due to corneal damages. However, for cultural reasons, there is a huge shortage of donor corneas in China. Acellular porcine corneal stromas (APCSs) can be used as corneal substitutes in lamellar keratoplasty for corneal ulcers. This study was conducted to analyze the results of APCS use for herpes simplex keratitis (HSK). METHODS: The study involved HSK patients who underwent keratoplasty with APCSs from February 2016 to October 2017 in the second affiliated hospital of Zhejiang University. Patient data were collected at 7 days, 1 month, 3 months, 6 months, and at the last follow-up (7-25 months) postoperative. The corneal transparency, neovascularization, visual acuity, and graft stability were observed. RESULTS: Thirteen patients with HSK including five patients with corneal perforation were included in this study, nine patients underwent deep anterior lamellar keratoplasty (DALK) and five perforation patients underwent double lamellar keratoplasty. There were nine men and four women with an average age of 62.5 ± 5.6 years old (ranging from 52 to 70 years old). The mean postoperative follow-up duration was 15.1 ± 5.8 months (ranging from 7 to 25 months). At the last visit, visual acuity improved in nine patients (69.2%) compared with preoperative (P = 0.008).The grafts of seven individuals (53.8%) were completely transparent or slightly opaque; their corneal transparency score had improved significantly compared with before the surgery (P = 0.010). Various degrees of neovascularization were present in 11 of the 13 patients (84.6%), most neovascularization gradually stabilized. Graft dissolution occurred in three eyes (23.1%) during the observation period, two underwent regrafting, the other one became stable after treatment. Three patients underwent second allograft transplantation, two of which encountered APCS graft dissolution and one of the patients requested a human donor allograft transplantation due to transparency issues despite the absence of adverse issues. CONCLUSION: Acellular porcine corneal stroma seems to be effective in the treatment of HSK and can be used in HSK with corneal perforation by using double lamellar keratoplasty in an emergency.

Therapeutic Challenges and Prognosis of Descemet's Membrane Endothelial Keratoplasty in Herpes Simplex Eye Disease.

PURPOSE: To describe the functional outcome, postoperative complications, and complication management of Descemet's membrane endothelial keratoplasty (DMEK) in corneal decompensation secondary to Herpes simplex eye disease (HED). METHODS: This retrospective interventional case series included 17 eyes that received DMEK for endothelial decompensation secondary to HED. Complete ophthalmological examination, including corrected-distance visual acuity (CDVA), anterior segment slit-lamp, and optical coherence tomography assessment, were performed preoperatively and postoperatively at regular follow-up intervals. Visual outcome and complication rates were compared with those of 72 consecutive eyes that received DMEK for Fuchs endothelial corneal dystrophy (FECD) and pseudophakic bullous keratopathy (PBK) during the same period. RESULTS: Mean follow-up time was 11.1 ± 5.9 months (range 6-27). CDVA improved from 1.16 ± 0.46 logMAR to 0.62 ± 0.44 logMAR (P = 0.001). Corneal pachymetry significantly decreased from 695 ± 53 µm at day 1 to 569 ± 88 µm at 2 months (P < 0.001). Postoperative complications occurred in 12 eyes, including primary graft failure (12%), endotheliitis (29%), corneal ulcers (35%), and cystoid macular edema (18%). Most complications occurred shortly after surgery, with a median delay of 2.5 months. In comparison, the complication rates for DMEK in FECD and PBK were significantly lower (no graft failure, P = 0.005; no endotheliitis, P < 0.001; no corneal ulcers, P < 0.001 and 3% cystoid macular edema, P = 0.046). CONCLUSIONS: DMEK surgery significantly improved CDVA in patients with endothelial decompensation due to HED. The rate of postoperative complications was higher than for FECD and PBK. Close follow-up is mandatory and the rate of postoperative inflammatory events suggests that patients should be kept on high doses of oral valacyclovir.

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.

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.

The outcome of penetrating keratoplasty for corneal scarring due to herpes simplex keratitis / O resultado da ceratoplastia penetrante para cicatriz de córnea consequente à ceratite por herpes simplex

ABSTRACT Purpose: To determine the outcomes of penetrating keratoplasty (PK) for treatment of corneal scarring caused by Herpes simplex virus (HSV) keratitis, and whether the corneal scar type affects treatment outcome. Methods: A retrospective analysis of patients who underwent PK for HSV-related corneal scarring between January 2008 and July 2011 was performed. The patients were categorized into two groups. Group 1 consisted of patients with a quiescent herpetic corneal scar and group 2 consisted of patients who developed a corneal descemetocele or perforation secondary to persistent epithelial defects with no active stromal inflammation. The mean follow-up was 21.30 ± 14.59 months. The main parameters evaluated were recurrence of herpetic keratitis, graft rejection, graft failure, visual acuity, and graft survival rate. Results: There were 42 patients in group 1 and 13 in group 2. Preoperative BCVA varied from hand movements to 0.7 logMAR. Postoperatively, 34 patients (61.8%) achieved visual acuity of 0.6 logMAR or more. Recurrence of HSV keratitis was noted in 12 (28.57%) eyes in group 1 and 4 (30.76%) eyes in group 2 (p=0.40). Graft rejection occurred in 4 eyes (9.52%) in group 1 and in 3 (23.07%) eyes in group 2 (p=0.58). The 1-, 2-, and 3-year graft survival rates were 91.9%, 76.0%, and 65.1% in group 1, and 89.5%, 76.0%, and 63.6% in group 2 (p=0.91), respectively. Conclusions: Although there were different recurrence and graft rejection rates for two groups, the graft survival rates at 3 years were similar. According to our results, without inflammation, corneal herpetic scarring with a descemetocele or perforation achieved similar graft survival rates with quiescent herpetic corneal scars.

RESUMO Objetivo: Determinar os resultados da ceratoplastia penetrante (PK) para o tratamento da cicatriz da córnea consequente à ceratite por Herpes simplex vírus (HSV), e se o tipo de cicatriz na córnea afeta o resultado cirúrgico. Métodos: Foi realizada análise retrospectiva dos pacientes, submetidos à PK para a cicatriz da córnea relacionados com o HSV entre janeiro de 2008 e julho de 2011. Os pacientes foram divididos em dois grupos. Grupo 1 consistiu de pacientes que tiveram cicatriz corneana herpética quiescente e grupo 2 consistiu de pacientes que desenvolveram descemetocele ou perfuração córnea secundária a defeitos epiteliais persistentes sem inflamação estromal ativa. O seguimento médio foi de 21,30 ± 14,59 meses. Os principais parâmetros avaliados foram recorrência de ceratite herpética, rejeição de enxerto, falência do enxerto, acuidade visual e taxa de sobrevida do enxerto. Resultados: Foram avaliados 42 pacientes do grupo 1 e 13 doentes do grupo 2. Acuidade visual pré-operatória variou de movimentos das mãos (HM) para 0,7 logMAR. No pós-operatório, 34 pacientes (61,8%) atingiram acuidade visual de 0,6 logMAR ou melhor. Doze olhos (28,57%) tiveram recorrência de HSV ceratite no grupo 1, e quatro olhos (30,76%) tiveram recorrência no grupo 2 (p=0,40). A rejeição do enxerto ocorreu em 4 olhos (9,52%) no grupo 1, e em 3 olhos do grupo 2 (23,07%; p=0,58), taxa de sobrevivência do enxerto foi de 91,9% a 1 ano, 76,0% aos 2 anos e 65,1% aos 3 anos no grupo 1, e 89,5% a 1 ano, 76,0% aos 2 anos e 63,6% aos 3 anos no grupo 2 (p=0,91). Conclusões: Embora diferentes taxas de recorrência e de rejeição do enxerto foram encontradas nos dois grupos, a taxa de sobrevida do enxerto em 3 anos foi semelhantes nos dois grupos. De acordo com nossos resultados, em casos sem inflamação, a cicatriz herpética da córnea com descemetocele ou perfuração demonstra as taxas de sobrevivência do enxerto semelhantes às da cicatriz corneana herpética quiescente.

Clinical evaluation of deep anterior lamellar keratoplasty using glycerol-cryopreserved corneal tissues for refractory herpetic stromal keratitis: An observational study.

The study aimed to evaluate the therapeutic effects of deep anterior lamellar keratoplasty (DALK) using glycerol-cryopreserved corneal tissues (GCCTs) in patients with refractive herpes simplex keratitis (HSK). This article was a retrospective, noncomparative, and interventional case series. Patients with HSK underwent DALK using GCCTs at Shanghai Tongji Hospital from 2012 to 2015. The best spectacle corrected visual acuity, recurrent inflammation, graft status, postoperative central graft thickness, and pre/postoperative complications were detected. The follow-up ranged from 24.4 ±â€Š5.6 months (range: 16-38 months). Overall, the best spectacle corrected visual acuity was increased from HM/10 cm to 0.15 before surgery to 0.41 ±â€Š0.14 (range: 0.1-0.8; P < 0.05) at 12 months postoperatively. Intraoperative microperforation occurred in 4 eyes (14.81%), and rejection episodes were encountered in 3 of 27 eyes (11.1%), and all of the eyes reversed. HSK recurred in 2 eyes (7.41%), 1 eye with repeated recurring HSK, and eventually led to perpetual corneal opacity and the patient refused a retransplantation. The mean entire corneal thickness was 0.519 ±â€Š0.018 mm (range: 0.5-0.56 mm) and the mean graft thickness was 0.405 ±â€Š0.033 mm (range: 0.35-0.47 mm) in the final follow-up. The DALK using GCCTs was proven to be an effective and safe therapy in treating refractory HSK.

High-Risk Corneal Graft Rejection in the Setting of Previous Corneal Herpes Simplex Virus (HSV)-1 Infection.

PURPOSE: The "high-risk phenotype" of corneal graft recipients is considered to be related to preexisting vascularization such as that associated with herpes simplex virus-1 (HSV-1) keratitis (HSK). The purpose of this study was to investigate the immunologic mechanisms underlying accelerated corneal graft rejection using a mouse model of HSK. METHODS: Herpes simplex virus type 1 keratitis was induced in BALB/c mice. Syngeneic and allogeneic (C57BL/6 mice) corneal grafts were performed in mice with HSK at different times after infection. Some grafts were performed on HSV-infected CD4 T cell-deficient BALB/c mice. Clinical, histologic, immunologic, and virus detection studies were performed on samples of cornea, draining lymph node (LN), and trigeminal ganglion (TG) cells. RESULTS: Corneal grafts in mice with HSK rejected with higher frequency and more rapid tempo compared with grafts in uninfected mice. In corneas with HSK and vascularization at the time of grafting, both syngeneic and allogeneic corneal grafts failed with similar frequency and tempo. However, in the absence of preexisting inflammation and vascularization, syngeneic grafts were accepted when the grafts were performed at a late time point after HSV infection (42 days), whereas allografts were rejected at this time. In contrast, syngeneic grafts in nonvascularized HSV-infected recipients failed if they were performed within 10 days of HSV infection, an effect that was dependent on CD4 T cells, as demonstrated using CD4 deficient mice. Importantly, a variably sustained but strongly positive anti-HSV T-cell response was detected in allografted HSK recipients with a similar but lesser response in syngeneic hosts. CONCLUSIONS: A previous HSV-1 corneal infection predisposes donor grafts to a high risk of failure by both innate and adaptive immune mechanisms in which an anti-HSV CD4 T-cell response plays a prominent role.

Conjunctival flap covering combined with antiviral and steroid therapy for severe herpes simplex virus necrotizing stromal keratitis.

Herpes simplex virus (HSV) necrotizing stromal keratitis is a common type of herpetic stromal keratitis (HSK). Antiviral medication alone cannot control the disease, and corticosteroid eye drops may aggravate the ulcer and result in corneal perforation. Amniotic membrane transplantation effectively treats superficial corneal ulcer resulting from necrotizing stromal HSK. However, the efficacy of this approach seems to be limited for more serious cases. This study presented the clinical treatment of severe HSV necrotizing stromal keratitis (ulcer depth greater than half of the corneal stroma) by conjunctival flap covering surgery in 25 patients (25 eyes) combined with antivirus and corticosteroid treatment at Shandong Eye Hospital from January 2007 to December 2013. Clinical results showed that the mean best spectacle-corrected visual acuity improved from preoperative 20/333 to postoperative 20/40 (P < 0.05). All patients recovered ocular surface stabilization. There was recurrence in two eyes, which was cured with antiviral medication. Conjunctival flap covering combined with antivirus and corticosteroid treatment is effective in treating severe HSV necrotizing stromal keratitis.

[Therapy refractory stromal Herpes keratitis under aciclovir]. / Therapierefraktäre stromale Herpeskeratitis unter Aciclovir.

We report the case of a patient with suspected ulcerating necrotizing herpetic stromal keratitis who showed no improvement despite intensive (amongst others antiherpetic) topical and systemic therapy. The ulcer healed following amniotic membrane transplantation and penetrating excimer laser keratoplasty was performed to improve visual acuity. The excision showed deep stromal proof of herpes simplex virus (HSV) type 1 antigens.

[Postoperative therapy after penetrating keratoplasty in herpes simplex keratitis]. / Herpes simplex keratitisekben végzett perforáló keratoplasztika posztoperatív terápiája.

INTRODUCTION: Keratitis due to herpes simplex infection is a common cause of corneal damage resulting in impaired vision. AIM: The aim of this study was to assess the outcome of penetrating keratoplasties in patients treated with systemic antiviral and immunosuppressive drugs. METHOD: The authors retrospectively analysed data of 12 patients who underwent penetrating keratoplasty. The average age at onset of the first keratitis preceding surgery was 18 years (between 5 and 40 years). The indication for surgery in 9 cases was to improve vision and in 3 patient to prevent corneal perforation. Nine patients were given both acyclovir and mycophenolate mofetil, as anti-viral agent and immunosuppressive treatment, respectively. Two patients were treated with anti-viral agent only while one patient received no systemic therapy. The average follow-up time was 53.1 months (between 16 and 84 months). RESULTS: Of the 9 patients who underwent surgery for improving vision, 8 patients had transparent grafts during follow up without vascularization. All eight patients had been treated with acyclovir and mycophenolate mofetil. In one patient who had no systemic treatment recurrence and graft rejection was observed. Only one of the surgeries performed in acute stage of inflammation resulted in a properly healed transparent graft without recurrence and rejection. In this patient acyclivir and mycophenolate mofetil therapy had been given previously. In two cases the preventive - full or partial - systemic treatment had no effect. The visual acuity improved in all cases. In three patients visual acuity was influenced by some other factors as well. CONCLUSIONS: The systemic acyclovir and mycophenolat mofetil therapy is fairly successful in perforating keratoplasty due to herpes simplex infection. Acyclovir decreases the risk of recurrence, while mycophenolate mofetil may prevent graft rejection. The timing of surgery is decisive; it leads to better results when performed in a scarred, noninflammatory state.