Outcome of Therapeutic Keratoplasty in Hopeless Microbial Keratitis Cases Otherwise Advised Evisceration.

PURPOSE: To study the outcome of therapeutic keratoplasty in severe microbial keratitis cases otherwise advised evisceration. METHODS: A retrospective, single-center clinical audit included 28 patients with severe microbial keratitis presenting from April 2014 to April 2016. Patients with microbial keratitis either affecting more than 2 quadrants of the limbus and/or cases with infections involving more than 180 mm of the cornea who were advised evisceration by more than one ophthalmologist were included. Cases with endophthalmitis were excluded. At 3 months, the outcome was "success" if resolution of infection occurred without recurrence and evisceration was not required. Success was termed "complete" if best vision was 6/24 or better and "partial" otherwise. The outcome was termed a "failure" if infection recurred in the graft or the eye was eviscerated. RESULTS: Mean age of the patients (male:female, 17:11) was 49.5 years, and the mean duration of symptoms before surgery was 28.6 days. Evisceration was required in 2/28 cases. The outcome was "success" in 22/28 cases (78.6%)-complete (10/22); partial (12/22)-and "failure" in 6/28 cases. The outcome was poorer in general in fungal keratitis (n = 16) than bacterial keratitis (n = 7). CONCLUSIONS: Primary evisceration is best avoided in infections limited to the anterior segment. Even in hopeless cases, every eye deserves a fair chance.

Surgical management of corneal infections.

PURPOSE OF REVIEW: The purpose of this review is to discuss the options for, and recent developments in, the surgical treatment of corneal infections. Although the mainstay of treatment of corneal infections is topical antimicrobial agents, surgical intervention may be necessary in a number of cases. These include advanced disease at presentation, resistant infections, and progressive ulceration despite appropriate treatment. Prompt and appropriate treatment can make the difference between a good outcome and loss of vision or the eye. RECENT FINDINGS: There are a number of surgical therapies available for corneal infections. 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. Although there are no completely novel therapies that have been developed recently, there have been incremental improvements in the existing treatment modalities making them more effective, easier, and safer. SUMMARY: Several options are available for surgically managing corneal infections. Ophthalmologists should select the optimal procedure based on the individual patient's situation. VIDEO ABSTRACT: http://links.lww.com/COOP/A20.

Indications for destructive ocular surgeries in Nigeria.

INTRODUCTION: Destructive ocular surgery (DOS) means eye loss. An audit of its indications would be useful in reducing its incidence. OBJECTIVE: To determine indications for destructive ocular surgeries. MATERIALS AND METHODS: The case records (files) of all the patients who had DOS in a tertiary health facility in Nigeria from January 2004 to December 2011 were reviewed retrospectively. The information extracted include the bio data, indication for DOS, type of surgery performed and history of the use of traditional eye medications (TEM) and willingness to use an artificial eye (AE). RESULTS: Thirty-seven patients had DOS. The mean age of the patients was 35.51years (SD 21.6) and the male to female ratio was 2.1:1. Evisceration was the commonest DOS performed , in 30 eyes (81.1 %). The most common indication for DOS was intraocular infection, in 15 eyes (40.5 %), followed, among others, by trauma in 13 (35.1 %) and malignant ocular tumours in 4 (10.8 %). There was association between age and indication for DOS (P = 0.032). Many patients, 15 (40.5%), used TEM and most, 34 (91.9%), refused an artificial eye (AE) after surgery. CONCLUSIONS: The most common indication for DOS in this study was intraocular infection. Evisceration was the commonest destructive eye surgery offered.

Streptococcus endophthalmitis outbreak after intravitreal injection of bevacizumab: one-year outcomes and investigative results.

PURPOSE: To report the 1-year clinical outcomes of an outbreak of Streptococcus endophthalmitis after intravitreal injection of bevacizumab, including visual acuity outcomes, microbiological testing, and compound pharmacy investigations by the Food and Drug Administration (FDA). DESIGN: Retrospective consecutive case series. PARTICIPANTS: Twelve eyes of 12 patients who developed endophthalmitis after receiving intravitreal bevacizumab prepared by a single compounding pharmacy. METHODS: Medical records of patients were reviewed; phenotypic and DNA analyses were performed on microbes cultured from patients and from unused syringes. An inspection report by the FDA based on site visits to the pharmacy that prepared the bevacizumab syringes was summarized. MAIN OUTCOME MEASURES: Visual acuity, interventions received, time to intervention, microbiological consistency, and FDA inspection findings. RESULTS: Between July 5 and 8, 2011, 12 patients developed endophthalmitis after intravitreal bevacizumab from syringes prepared by a single compounding pharmacy. All patients received initial vitreous tap and injection, and 8 patients (67%) subsequently underwent pars plana vitrectomy (PPV). After 12 months follow-up, outcomes have been poor. Seven patients (58%) required evisceration or enucleation, and only 1 patient regained pre-injection visual acuity. Molecular testing using real-time polymerase chain reaction, partial sequencing of the groEL gene, and multilocus sequencing of 7 housekeeping genes confirmed the presence of a common strain of Streptococcus mitis/oralis in vitreous specimens and 7 unused syringes prepared by the compounding pharmacy at the same time. An FDA investigation of the compounding pharmacy noted deviations from standard sterile technique, inconsistent documentation, and inadequate testing of equipment required for safe preparation of medications. CONCLUSIONS: In this outbreak of endophthalmitis, outcomes have been generally poor, and PPV did not improve visual results at 1-year follow-up. Molecular testing confirmed a common strain of S. mitis/oralis. Contamination seems to have occurred at the compounding pharmacy, where numerous problems in sterile technique were noted by public health investigators.

Prevalence of Human Immunodeficiency Virus Seropositivity among Eye Surgical Patients at a Rural Eye Care Facility in South-Eastern Nigeria

Purpose: To determine the prevalence of human immunodeficiency infection among patients who underwent surgery at a rural eye care facility in southeastern Nigeria. Materials and Methods: A retrospective chart review was performed for all patients who had undergone surgery and a pre-operative Human Immunodeficiency Virus (HIV) test; between August 2008 and July 2009 at the Eye unit of the Presbyterian Joint Hospital; Ohaozara; Ebonyi State; Nigeria. Data were analyzed for age; sex; type of surgery and HIV status. Frequency; percentage and 95confidence intervals (CI) were calculated with univariate analysis and the parametric method. Results: A total of 380 cases were reviewed comprised of 228 males and 152 females (M:F= 1.5:1).The mean age of the cohort is 56 years (range; 4 years to 91 years). Fourteen patients (3.7; 95confidence interval 1.8 - 5.6) were HIV positive. Conclusion: A high HIV sero-prevalence was reported in our study. Infection-control precautionary measures are indicated to minimize risk of HIV transmission to ophthalmic surgeons and allied health-workers

Deep anterior lamellar keratoplasty using acellular corneal tissue for prevention of allograft rejection in high-risk corneas.

PURPOSE: To determine whether deep anterior lamellar keratoplasty (DALK) using acellular glycerol-cryopreserved corneal tissue (GCCT) could prevent allograft rejection in high-risk corneas. DESIGN: Prospective, randomized, comparative study. SETTINGS: The Eye Hospital, Wenzhou Medical College, Zhejiang, China. STUDY POPULATION: All patients with herpes simplex virus keratitis, bacterial keratitis, fungal keratitis, or ocular burn, who were eligible as per study design, were invited to participate. OBSERVATION PROCEDURES: According to randomized block design, all patients received either GCCT or fresh corneal tissue (FCT) during DALK. Best-corrected visual acuity (BCVA), slit-lamp microscopy, and in vivo confocal microscopy examinations at 1 week and 1, 3, 6, 12, and 24 months after surgery were analyzed. Kaplan-Meier survival analysis was used to evaluate graft survival rate. MAIN OUTCOME MEASURES: Therapeutic success, 2-year rejection-free graft survival rate and 2-year graft survival rate, in vivo confocal microscopy results, BCVA, and endothelial cell density. RESULTS: Postoperative BCVA of 20/40 or better at the last follow-up visit was achieved in 57.6% (19/33) of eyes in the GCCT group and in 54.8% (17/31) of the FCT group. No graft rejection occurred in the GCCT group, while in the FCT group 10 episodes of stromal rejection developed in 7 eyes. Overall, the rejection-free graft survival rate at 2 years was significantly higher in the GCCT group as compared with the FCT group (100.0%, 78.8% respectively, P = .006). CONCLUSIONS: Deep anterior lamellar keratoplasty using acellular glycerol-preserved cornea could prevent allograft rejection and promote graft survival rate in high-risk corneas.

Sequential therapeutic penetrating keratoplasty with cryopreserved and fresh corneal tissue for severe infectious keratitis: a case-control study.

PURPOSE: Sequential therapeutic penetrating keratoplasty (TPK) using a cryopreserved cornea followed soon after by a fresh optical grade cornea for severe infectious keratitis may improve the survival of the optical graft. The aim of this study was to compare the therapeutic efficacy, visual outcomes, and graft survival for sequential TPK against TPK using a fresh optical grade cornea alone. METHODS: This was a retrospective case-control study. Case records were reviewed for clinical and surgical outcomes. RESULTS: Thirty-two eyes of 32 patients were included. Ten eyes underwent sequential TPK (TPK cases), and there were 22 age- and sex-matched controls, which underwent TPK with optical grade tissue alone. The mean interval between the TPK with the frozen cornea and the subsequent optical keratoplasty in the TPK cases was 16.8 ± 12.9 days. Therapeutic success, defined as the eradication of the primary infection, was achieved in all the TPK cases but only in 13 controls (59.1%) (P = 0.06). Graft survival at 1 year was better in the TPK cases than the controls (72.9% vs 53.8%). An improvement in Snellen acuity by at least 2 lines was more likely in the TPK cases than the controls (80% vs 14%; P = 0.001). CONCLUSIONS: Sequential TPK is an effective surgical therapy for active severe infectious keratitis and also helps to conserve valuable optical grade corneal tissue.

Indications and outcomes of deep anterior lamellar keratoplasty in children.

PURPOSE: To report our experience of deep anterior lamellar keratoplasty (DALK) in children. DESIGN: Retrospective case note review. PARTICIPANTS: Nine patients (13 eyes) aged from 13 weeks to 14 years, 11 months at the Clinical and Academic Department of Ophthalmology, Great Ormond Street Hospital for Children National Health Service (NHS) Trust, London, United Kingdom. METHODS: A study of all pediatric patients undergoing DALK from February 2002 to October 2008 was undertaken. Deep anterior lamellar keratoplasty was attempted in 9 children (13 eyes); the procedure was successful in 11 eyes, and 2 eyes progressed to penetrating keratoplasty (PKP). One eye underwent repeat DALK. Preoperative examination included electrophysiology, ultrasound biomicroscopy (UBM), and slit-lamp biomicroscopy. MAIN OUTCOME MEASURES: Complications and visual acuity at last follow-up. RESULTS: Five patients had mucopolysaccharidoses (MPS), 3 patients had scarring presumed to be infectious, and 1 patient had keratoconus. Because of the failure of follow-up and loose sutures, 1 child with MPS had an epithelial rejection and the operation was repeated successfully. All grafts showed good graft clarity 10 to 80 months after grafting with visual acuities ranging from 0.28 to 1.0 logarithm of the minimum angle of resolution. Two children with nonspecific causes of scarring showed good visual acuities 24 to 51 months post-DALK. Two children who had conversion to PKP were lost to follow-up because they had moved abroad. In 4 of the 5 children with MPS, established techniques of DALK could not be performed because of excessive glycosaminoglycans (GAGs) in the stroma. Ultrasound biomicroscopy was used to guide trephination depth in the first instance. In 1 child with MPS, viscodissection was successfully used. All clinically diagnosed scars were histologically confirmed, and electron microscopy of corneal buttons confirmed the diagnosis in patients with MPS. CONCLUSIONS: Deep anterior lamellar keratoplasty should be considered in children with MPS and partial-thickness scars. In MPS, viscodissection and the "big bubble" technique may not be useful if there are excessive GAGs in the stroma. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

Therapeutic keratoplasty for microbial keratitis.

PURPOSE OF REVIEW: The purpose of this review is to provide an update of peer-reviewed literature published over the previous 2 years on various aspects of therapeutic keratoplasty. RECENT FINDINGS: Therapeutic keratoplasty has a definitive role in the management of progressive microbial keratitis refractory to medical therapy. The primary aim of the procedure is to eliminate the infectious disease process and establish the integrity of the globe. This procedure offers a microbiological cure rate of up to 100% in bacterial keratitis; recurrence of infection remains a concern following fungal infections and Acanthamoeba keratitis. Newer techniques like corneal debulking allow maximal preservation of the iris tissue in cases of perforated corneal ulcers. Lamellar procedures are emerging as promising alternatives to the full thickness graft in cases of infectious keratitis sparing the Descemet's membrane. In addition to adept intraoperative skills, intensive postoperative treatment and meticulous follow-up are pivotal to ensure success of a therapeutic graft. SUMMARY: Therapeutic keratoplasty is a challenging procedure and is associated with a poor prognosis for graft survival as compared with the optical grafts. The recent advances in lamellar keratoplasty and antimicrobial therapy contribute to the success in terms of microbiological cure and improved visual outcomes.

Outcomes of therapeutic deep lamellar keratoplasty and penetrating keratoplasty for advanced infectious keratitis: a comparative study.

PURPOSE: To compare the therapeutic success, visual outcomes, complications, and graft survival rates of therapeutic deep anterior lamellar keratoplasty (TDALK) and therapeutic penetrating keratoplasty (TPK) for advanced infectious keratitis. DESIGN: Retrospective, comparative study. PARTICIPANTS: One hundred twenty-three patients (126 eyes) with medically uncontrolled infectious keratitis of bacterial, fungal, or acanthamoeba etiologies who underwent TDALK (n = 26) or TPK (n = 100 eyes; 80 nonperforated ulcers; 20 perforated ulcers; mean follow-up in TDALK, 12.9 months; in TPK, 21.3 months). METHODS: We performed TDALK for infections confined to the corneal stroma and the technique used was either manual lamellar dissection or Anwar's big bubble technique for total stromal removal. Therapeutic penetrating keratoplasty was performed for either nonperforated or perforated ulcers. Comparison with respect to recurrence of infection, visual acuity, graft survival, and complications was made. Baseline characteristics of the patients were analyzed using the chi-square test. Kaplan-Meier survival analysis was used to evaluate graft survival. MAIN OUTCOMES MEASURES: Therapeutic success (eradication of infection) or therapeutic failure (recurrence of original infection in cornea or sclera, or as endophthalmitis), graft survival (clarity), and best-corrected visual acuity (BCVA). RESULTS: Therapeutic success rate of 84.6% was achieved in the TDALK group and 88% in the TPK group (P = 0.74); of the 12 eyes with recurrence of infection in the TPK cohort, 6 developed endophthalmitis with poor outcomes. A BCVA of > or =6/9 was achieved in 50% of patients in the TDALK group and 20.2% in the TPK group (P = 0.01). Mean improvement of acuity was 7.27 lines in the TDALK group and 4.76 lines in the TPK group (P = 0.01). Kaplan-Meier survival analysis at 1 year showed better graft survival for TDALK (90%) compared with TPK (78.4%). CONCLUSIONS: For medically unresponsive infectious keratitis, TDALK may be considered instead of TPK yielding similar graft survival, without an increased risk of disease recurrence.

Resuturing following penetrating keratoplasty: a retrospective analysis.

AIM: To examine the clinical profile of cases requiring resuturing following penetrating keratoplasty (PKP) at a tertiary care eye hospital. METHODS: The medical records of 947 consecutive patients who had undergone PKP between 1998 and 2006 were reviewed retrospectively and cases that were resutured during this period were analysed. The main parameters studied were indications for PKP, suturing techniques, causes of resuturing, visual acuity outcome and post-resuturing complications. RESULTS: The incidence of resuturing was 5.4% (51 eyes). The number of cases requiring resuturing was higher in corneal grafts performed for microbial keratitis (12%) than those for keratoconus (10%) and corneal endothelial decompensation (2.5%; p = 0.08). Wound dehiscence was the leading cause for resuturing (43%), followed by loose or broken sutures (37.3%). The most common complications after resuturing were occurrence of microbial keratitis (7.8%) and graft failure (5.9%). DISCUSSION: Resuturing may have to be performed more commonly for corneal transplantation surgery done for microbial keratitis and keratoconus. The major indications for resuturing are wound dehiscence and loose/broken sutures.

Camphor-related self-inflicted keratoconjunctivitis complicating delusions of parasitosis.

PURPOSE: To report a case of camphor-related self-inflicted keratoconjunctivitis secondary to delusions of parasitosis. METHODS: A 61-year-old man with delusions of parasitosis suffered from camphor-related self-inflicted ocular trauma that manifested with corneal epithelial defects and secondary anterior chamber reaction. Two episodes of exacerbation of the ocular conditions related to the use of camphor occurred. The left eye had secondary infection with Sternotrophomonas maltophilia and Staphylococcus aureus in the second episode of exacerbation. RESULTS: The right eye recovered well with the treatment of topical lubricants and corticosteroids and had best-corrected visual acuity (BCVA) of 20/25. The infection of the left eye led to corneal perforation, necessitating penetrating keratoplasty; BCVA was hand motions because of a mature cataract. Olanzapine therapy for 1 month to decrease the delusions of parasitosis and 24-hour watch to prevent the use of camphor led to the resolution of self-inflicted keratoconjunctivitis in the patient. CONCLUSIONS: Delusions of parasitosis may lead to vision-threatening self-inflicted ocular trauma. This may be the first case report of pure camphor-related self-inflicted toxic keratoconjunctivitis.

Factors predicting unsuccessful big bubble deep lamellar anterior keratoplasty.

PURPOSE: To evaluate the role of corneal structural resistance as a surgical failure factor in deep lamellar keratoplasty (DLK). METHOD: A total of 10 eyes of 10 patients underwent DLK at the Ophthalmic Hospital in Rome. The big bubble technique was performed for deep stromal dissection by air injection. Seven patients were affected by advanced keratoconus and corneal thinning ranging from 441 to 235 microm. Two patients were affected by central corneal opacity from herpetic keratitis, and one patient suffered from corneal leucoma caused by bacterial keratitis. Clinical follow-up comprising final astigmatism and visual acuity findings were evaluated with a minimum follow-up of 12 weeks. RESULTS: DLK was successfully performed in eight eyes, five of which were affected by moderate to advanced keratoconus and three by post-infective corneal opacity. In these patients preoperative ultrasonic pachymetry ranged between 441 and 287 microm. In the remaining two patients a perforation of the Descemet's membrane (DM) occurred while attempting to separate it from the overlying stroma by the big bubble technique, requiring a penetrating keratoplasty (PK) to be performed. In both cases preoperative ultrasonic pachymetry was below 250 microm. Both perforations occurred at a different site than the needle site and at the operative time of the big-bubble injection. DISCUSSION: An ultrastructurally weakened DM may suffer a loss of resistance to a stressing force, becoming unable to tolerate the big bubble technique, and thus being perforated. Since the weakening of the DM is related to end-stage keratoconus corneal thinning, the preoperative corneal thickness rather than the surgeon's ability can play a major role in surgical failure of DLK. Our study reveals a very high risk of perforation of the DM when pre-operative total pachymetry is below limit of 250 microm.

Did the spectrum of endophthalmitis change? A study comprising 13 years experience with operative therapy of endophthalmitis.

PURPOSE: The authors wondered whether the spectrum of endophthalmitis and the type of therapy had changed. METHODS: Files of patients who were operated upon for endophthalmitis between 1988 and 2000 were retrospectively analyzed. They were divided into Group 1 (operated upon 1988 to 1994) and Group 2 (1995 to 2000). RESULTS: Group 1 consisted of 83 patients (43.4% female, mean age 63.9 years), Group 2 of 108 (38.9% female, mean age 64.6 years). Bilateral endophthalmitis occurred in 8.4% of Group 1 patients (3.7% of Group 2 patients). Patients in both groups took on average 1.2 drug types against various internal diseases. The mean interval between first symptoms and presentation in the clinic was 45.7 days in Group 1 (19 days in Group 2; difference statistically significant). There were 63% (Group 1) (70% [Group 2]) cases of postoperative endophthalmitis, among them 58% (Group 1) (63% [Group 2]) after cataract extraction, 6% (Group 1) (5% [Group 2]) after glaucoma surgery, 20% (Group 1) (17% [Group 2]) endogenous and 17% (Group 1) (13% [Group 2]) post traumatic. In Group 2 slightly more Gram-negative bacteria were found. As an initial procedure the following were performed: vitrectomy (70% [Group 1], 88% [Group 2]), removal of crystalline lens (11% [Group 1], 10% [Group 2]), removal of pseudophakos (2% [Group 1], 12% [Group 2]), opening of posterior capsule (1% [Group 1], 9% [Group 2]), and anterior chamber irrigation (36% [Group 1], 43% [Group 2]), often combining procedures. There were significantly more vitrectomies and openings of the posterior capsule in Group 2. Neither the spectrum of secondary and tertiary procedures nor the reasons for such surgery differed in both groups. Neither visual acuity at initial presentation (0.1) nor at final follow-up (0.3) differed between the two groups. The rate of enucleation was less in Group 2 (6% versus 11%) although not statistically significantly. CONCLUSIONS: In Group 2 there were slightly more Gram-negative bacteria and the time interval between initial symptoms and presentation in the clinic had decreased. This can be interpreted as an increase in the severity of the endophthalmitis cases. The final visual acuity was identical in both groups, the enucleation rate improved.

Claritromicina oral como opción terapéutica en endoftalmitis post-quirúrgicas tardías / Oral clarithromycin as a treatment option in chronic post-operative endophthalmitis

Objetivos: Evaluar la respuesta al tratamiento médico con claritromicina oral de pacientes con endoftalmitis post-quirúrgica crónica.Métodos: Este estudio prospectivo se desarrolló durante el período comprendido entre enero de 1999 y septiembre de 2003. Se incluyeron pacientes con diagnóstico de endoftalmitis crónica de comienzo tardío que tuvieran etiología bacteriana. Se les administró claritromicina oral en 2 tomas diarias de 500 mg durante 14 días. Se registraron la agudeza visual inicial y final, la etiología, el tiempo de aparición del cuadro, el tiempo de demora de la instauración del tratamiento y el tiempo de seguimiento post tratamiento. Acorde a la respuesta al mismo los pacientes fueron distribuidos en 3 grupos: 1) Respuesta total, 2) respuesta parcial, 3) respuesta negativa.Las comparaciones estadísticas se realizaron mediante t de Student y la prueba exacta de Fisher según se consideró necesario.Resultados: Fueron diagnosticados 15 casos de endoftalmitis crónica (11 por Propionibacterium acnes y 4 por Staphylococcus epidermidis).Se observó respuesta total en 4 casos, parcial en 4 y negativa en 7.La comparación de las proporciones de pacientes con agudeza visual final mayor a 0,5 entre el grupo de respuesta total y el de respuesta negativa fue significativo (prueba exacta de Fisher= 0,0454 p=0,05). En cambio la misma comparación entre el grupo de respuesta total y el de respuesta parcial fue no significativo.Conclusiones: El tratamiento médico con claritromicina oral puede ser útil en algunos pacientes con endoftalmitis post-quirúrgica crónica

Purpose: To assess the outcome of medical treatment with oral clarithromycin in patients with chronic post-surgical endophthalmitis. Methods: This prospective study was performed between January 1999 and September 2003. Patients with a diagnosis of chronic post-surgical endophthalmitis of bacterial etiology were included. All received 500 mg of oral clarithromycin twice a day for 14 days. The initial and final visual acuity, etiology, post-surgical time of presentation, treatment-delay time, and follow up were recorded. According to the treatment results, patients were distributed into 3 separate groups: 1) complete response, 2) partial response, 3) no response. Data from these groups were compared by means of the Student’s t test and Fisher exact test, depending on which was considered most suitable. Results: Fifteen cases of chronic endophthalmitis (11 of Propionibacterium acnes, 4 of Staphylococcus epidermidis) were diagnosed. A complete response was observed in 4 cases, partial response in 4 cases, and no response in 7 cases. Final visual acuity greater than 0.5 was significantly more likely in the complete response group when compared with the no response group (Fisher exact test = 0.0454, p=0.05), however, the same comparison between the complete response group and the partial response group was not significant. Conclusion: Medical treatment with oral clarithromycin could be useful in some patients with chronic post-surgical endophthalmitis

Keratocyte loss in corneal infection through apoptosis: a histologic study of 59 cases.

BACKGROUND: Keratocyte loss by apoptosis following epithelial debridement is a well-recognized entity. In a study of corneal buttons obtained from patients of corneal ulcer undergoing therapeutic keratoplasty, we observed loss of keratocytes in the normal appearing corneal stroma, surrounding the zone of inflammation. Based on these observations, we hypothesized that the cell loss in the inflammatory free zone of corneal stroma is by apoptosis that could possibly be a non-specific host response, independent of the nature of infectious agent. METHODS: To test our hypothesis, in this study, we performed Terminal deoxyribonucleotidyl transferase-mediated d-Uridine 5" triphosphate Nick End Labelling (TUNEL) staining on 59 corneal buttons from patients diagnosed as bacterial, fungal, viral and Acanthamoeba keratitis. The corneal sections were reviewed for morphologic changes in the epithelium, stroma, type, degree and depth of inflammation, loss of keratocytes in the surrounding stroma (posterior or peripheral). TUNEL positivity was evaluated in the corneal sections, both in the zone of inflammation as well as the surrounding stroma. A correlation was attempted between the keratocyte loss, histologic, microbiologic and clinical features. RESULTS: The corneal tissues were from 59 patients aged between 16 years and 85 years (mean 46 years) and included fungal (22), viral (15), bacterial (14) and Acanthamoeba (8) keratitis. The morphological changes in corneal tissues noted were: epithelial ulceration (52, 88.1%), destruction of Bowman's layer (58, 99%), mild to moderate (28; 47.5%) to severe inflammation (31; 52.5%). Morphologic evidence of disappearance or reduced number of keratocytic nuclei in the corneal stroma was noted in 49 (83%) cases; while the TUNEL positive brown cells were identified in all cases 53/54 (98%), including cases of fungal (19), bacterial (14), viral (13), and Acanthamoeba keratitis. TUNEL staining was located mostly in the deeper stroma and in few cases the peripheral stroma. TUNEL positivity was also noted with the polymorphonuclear infiltrates and in few epithelial cells (10 of 59, 17%) cases, more with viral infections (6/10; 60%). CONCLUSIONS: We report apoptotic cell death of keratocytes in the corneal stroma in infectious keratitis, a phenomenon independent of type of infectious agent. The inflammatory cells in the zone of inflammation also show evidence of apoptotic cell death. It could be speculated that the infective process possibly triggers keratocyte loss of the surrounding stroma by apoptosis, which could possibly be a protective phenomenon. It also suggests that necrotic cell death and apoptotic cell deaths could occur simultaneously in infective conditions of the cornea.