Corneal Endotheliitis Research Articles

Pharmacokinetics of ganciclovir eye drops: a comparative study of solutions prepared from ganciclovir for intravenous infusion and ganciclovir gel.

To evaluate the pharmacokinetics of ganciclovir eye drops by comparing solutions prepared from ganciclovir for intravenous infusion and ganciclovir gel and to assess the impact of systemic administration on drug levels in ocular tissues and serum. Experimental study design. Ganciclovir solutions (0.5% and 1.0%) prepared by diluting DENOSINE ® IV Infusion in saline and 0.15% ganciclovir gel (Virgan®) were topically administered in rabbit eyes, with and without concomitant systemic administration of ganciclovir. The concentrations of ganciclovir in the corneal epithelium, stroma, and endothelium, aqueous humor; and blood plasma were analyzed by high-performance liquid chromatography (HPLC). The ganciclovir solutions (0.5% and 1.0%) maintained therapeutic ganciclovir levels in the corneal endothelium above the effective dose required for 50% inhibition (ED50) up to 6h, albeit with a swift decline thereafter. The 0.15% ganciclovir gel maintained higher therapeutic concentrations in the corneal endothelium for up to 12h, exceeding the ED50. Serum concentrations of ganciclovir were significantly elevated in the groups receiving combined systemic administration. Topical application of 0.15% ganciclovir gel maintained high endothelial concentrations, well above the therapeutic threshold, with or without systemic administration. Furthermore, the observed increase in ganciclovir levels within the plasma and aqueous humor following systemic administration posits it as a viable strategy for severe cases of cytomegalovirus corneal endotheliitis or those inadequately managed by local treatments alone.

Authors’ Reply to Letter to the Editor– in Response to: Comment on Dheyab AM et al. “Long-Term Efficacy of Oral Valganciclovir in Presumed Cytomegalovirus Unilateral Hypertensive Anterior Uveitis”

ABSTRACT The clinical diagnosis of presumed cytomegalovirus hypertensive anterior uveitis was based on the following criteria: 1) Recurrent episodes of unilateral hypertensive anterior uveitis characterized by acute elevation of intraocular pressure, a few medium-sized or mutton-fat keratic precipitates and mild anterior chamber reaction. These findings might be associated with corneal endotheliitis and iris atrophy. 2) Posterior synechiae and vitreous involvement are typically absent. 3) Intact corneal sensation.

Cytokine analysis of aqueous humor in patients with cytomegalovirus corneal endotheliitis.

To evaluate cytokine levels of aqueous humor in patients with cytomegalovirus (CMV) corneal endotheliitis and their relationships with CMV DNA load. 44 aqueous humor samples were obtained from 26 patients with CMV corneal endotheliitis at various stages of treatment. 33 samples obtained from cataract patients during the same period were selected as a control group. Each sample was used to measure the concentration of the CMV DNA load using real-time quantitative polymerase chain reaction, and to examine the levels of IL-6, IL-8, IL-10, MCP-1, VCAM-1, VEGF, IP-10, G-CSF, ICAM-1 and IFN-γ using a cytometric bead array. All 10 cytokines were found to have statistically significant differences between the CMV endotheliitis and cataract groups. The Spearman correlation test showed that the concentration of CMV DNA load was significantly associated with the levels of IL-6 (P = 0.005, r = 0.417), IL-8 (P < 0.001, r = 0.514), IL-10 (P < 0.001, r = 0.700), MCP-1 (P = 0.001, r = 0.487), VEGF (P < 0.001, r = 0.690), IP-10 (P = 0.001, r = 0.469), G-CSF (P < 0.001, r = 0.554) and ICAM-1 (P < 0.001, r = 0.635), but not significantly associated with VCAM-1 (P = 0.056) and IFN-γ (P = 0.219). There was a combined innate and adaptive immune response in aqueous humor in patients with CMV endotheliitis. Levels of multiple cytokines were significantly correlated with viral particle. Cytokines are potential indicators to help diagnose CMV endotheliitis, evaluate disease activity and assess treatment response.

Clinical applications of in vivo confocal microscopy enhance the detection and management of ocular surface disease in dogs and cats.

In vivo confocal microscopy (IVCM) is a unique imaging technique that permits noninvasive evaluation of the ocular surface on the cellular level. High-resolution images of all layers of the cornea are obtained in real-time with IVCM, and the acquired images are often comparable to ex vivo histochemical analysis of corneal biopsy specimens. The basic morphological features of the healthy living cornea as viewed by IVCM are reported in many domestic animal species, and the number of published descriptions of ocular surface pathologies in companion animals is progressively expanding. There is great potential for IVCM to improve the detection, characterization, and management of diverse ocular surface diseases in companion animals. This review summarizes several established and emerging clinical applications of IVCM in companion animal ocular surface disease, including infectious keratitis, corneal foreign bodies, corneal dystrophies and degenerations, ocular surface masses, corneal endotheliitis, pigmentary keratitis, and evaluation of corneal nerves.

A Case of Atypical Cytomegalovirus Corneal Endotheliitis after Intravitreal Triamcinolone Injection

Purpose: We present an atypical case of cytomegalovirus corneal endotheliitis after intravitreal triamcinolone injection.Case summary: A 61-year-old man presented with decreased visual acuity after intravitreal triamcinolone (Maqaid®, Wakamoto Pharmaceutical Co., Ltd., Tokyo, Japan) injection for cystoid macular edema following cataract surgery. Ocular examination revealed elevated intraocular pressure, diffuse keratic precipitates with corneal edema, and anterior chamber inflammation. These findings were suggestive of viral corneal endotheliitis. Polymerase chain reaction analysis of the anterior chamber aqueous humor detected cytomegalovirus DNA. Consequently, the patient was diagnosed with cytomegalovirus corneal endotheliitis. He was treated with oral valganciclovir (Valcyte®, Roche, Basel, Switzerland) at a dose of 1,800 mg/day for 3 weeks as an induction phase, followed by 900 mg/day for 3 weeks as a remission phase. This treatment regimen led to significant improvement in corneal edema and anterior chamber inflammation with complete restoration of visual acuity.Conclusions: It is important to note that cytomegalovirus endotheliitis can occur after intravitreal triamcinolone injection and can present in an atypical rather than a typical form.

Overview of Cytomegalovirus Ocular Diseases: Retinitis, Corneal Endotheliitis, and Iridocyclitis.

Cytomegalovirus (CMV) infection is a significant clinical concern in newborns, immunocompromised patients with acquired immunodeficiency syndrome (AIDS), and patients undergoing immunosuppressive therapy or chemotherapy. CMV infection affects many organs, such as the lungs, digestive organs, the central nerve system, and eyes. In addition, CMV infection sometimes occurs in immunocompetent individuals. CMV ocular diseases includes retinitis, corneal endotheliitis, and iridocyclitis. CMV retinitis often develops in infected newborns and immunocompromised patients. CMV corneal endotheliitis and iridocyclitis sometimes develop in immunocompetent individuals. Systemic infections and CMV ocular diseases often require systemic treatment in addition to topical treatment.

Stromal Keratitis Associated With Cytomegalovirus Anterior Uveitis.

Human cytomegalovirus (CMV) has commonly been reported as a cause of anterior uveitis and corneal endotheliitis. Unlike its other herpetic family members, herpes simplex virus and varicella zoster virus, involvement of the corneal stroma in CMV is uncommon. In this case series, we describe patients with CMV stromal keratitis. This was a retrospective chart review of patients seen at a tertiary referral center from 1999 to 2023 with stromal keratitis who tested positive for CMV by directed polymerase chain reaction of aqueous fluid or corneal tissue. This series describes 5 patients, 4 of whom presented with anterior uveitis and stromal keratitis and were confirmed to be positive for CMV through the polymerase chain reaction of aqueous fluid. The fifth patient experienced recurrent corneal graft failures, with the most recent failed graft being positive for CMV based on immunohistochemical stains of the corneal stroma. The average age of patients was 62 years (range 36-80 years). Only 1 patient (20%) exhibited elevated intraocular pressure with stellate keratic precipitates at the initial presentation, whereas 3 other patients (60%) had a known history of glaucoma. Uveitis specialists are well aware of CMV as a cause of recurrent, hypertensive anterior uveitis but should also consider CMV in cases featuring stromal keratitis. The corneal endothelium may serve as a reservoir for both anterior uveitis and development of corneal stromal inflammation as demonstrated by the immunohistopathology exhibited in 1 case.

The Impact of Severe COVID–19 on Corneal Endothelial Cells–Analysis of the In Vivo Noncontact Specular Microscopy

ABSTRACT Purpose This study aimed to investigate the effects of severe COVID-19 infection on the corneal endothelium via in vivo specular microscopy. Methods This was an observational, prospective, and controlled study including 56 eyes of 56 severe COVID-19 patients, compared to after-recovery and 56 eyes of 56 age- and gender-matched healthy controls. Results Endothelial cell density was lower in the active disease period compared to healthy controls (p = .001) and decreased even more after recovery (p < .0001). After recovery, the average cell area and coefficient of variation were higher compared to the active disease period (p < .0001 and p = .008, respectively) and the healthy controls (for both, p < .0001), whereas hexagonality was lower (p < .0001). Central corneal thickness increased in the active disease period compared to after recovery (p < .0001) and healthy controls (p = .002). Conclusions These results may be due to direct host-virus interaction or linked to immune dysregulation, subclinical corneal endotheliitis, or still yet a viral-mediated inflammation.

Epstein-Barr Virus Keratouveitis-Induced Malignant Glaucoma After Penetrating Keratoplasty: A Case Report and Literature Review

ABSTRACT Purpose To report a case of Epstein-Barr virus (EBV) keratouveitis-induced malignant glaucoma after repeat penetrating keratoplasty (PK). Methods Retrospective review of the patient’s medical records and review of literature on EBV corneal endotheliitis and/or anterior uveitis. Results A 78-year-old Thai female patient presented with a markedly edematous corneal graft, dense pigmented keratic precipitates, fibrinous anterior chamber reaction, uniformly flat anterior chamber, and ocular hypertension of 55 mmHg in the left eye on the first day after the third PK. An aqueous tap for polymerase chain reaction analysis was positive for EBV DNA but negative for other herpesviruses. The patient was diagnosed with EBV endotheliitis and anterior uveitis-induced malignant glaucoma; and successfully treated with oral valacyclovir and topical 2% ganciclovir eye drops. Conclusions EBV endotheliitis and anterior uveitis can induce malignant glaucoma following PK. A high index of suspicion is required when a patient has a history of unexplained multiple graft rejections.

Overview and update on cytomegalovirus-associated anterior uveitis and glaucoma.

Cytomegalovirus anterior uveitis is the most common ocular inflammatory disease caused by cytomegalovirus infection. It mainly occurs in middle-aged males with competent immunologic function, and the incidence is higher in Asia. The clinical manifestations vary from Posner-Schlossman syndrome and corneal endotheliitis to Fuchs uveitis syndrome, and are often accompanied by intraocular hypertension. Secondary glaucoma is a potentially blinding ocular complication with a pathogenesis that includes complicated immunological factors, intraocular inflammation, different types of angle abnormalities, and the administration of steroids, which may result in physical discomfort and visual impairment. Diagnostic tests, such as the polymerase chain reaction, optical coherence tomography, ocular microscopy, and confocal microscopy, might help in identifying anterior uveitis caused by other viruses. Combinations of antiviral medications and anti-inflammatory agents are effective treatments. If pharmacological therapy cannot reduce intraocular pressure or slow the progression of glaucomatous optic neuropathy, surgical intervention is required as a last resort.

Chinese expert consensus on diagnosis and treatment of viral corneal endotheliitis (2023)

Viral corneal endotheliitis, a blinding corneal disease, is often misdiagnosed due to the diverse clinical manifestations, complex conditions, unclear diagnostic criteria, and limited methods of ocular virus detection. In addition, there is still a lack of unified and standardized treatment for viral corneal endotheliitis. The consensus, basing upon the latest research progress and expert recommendations regarding the clinical care of patients with viral corneal endotheliitis, targets to offer best practice advice for the clinical management of viral corneal endotheliitis and has been fully discussed by the experts of the Ocular Infection Group of Chinese Ophthalmologist Association.

Presumed viral endotheliitis following topical mitomycin C for the treatment of ocular surface squamous neoplasia in a glaucoma patient

Corneal endotheliitis and ocular surface neoplasia are known to be associated with altered immune status especially in the elderly. We reviewed an interesting case where endotheliitis occurred for the first time while on topical chemotherapy for ocular surface neoplasia in a patient with glaucoma. We have addressed the practical concerns in decision-making given multiple ocular comorbidities and highlighted a successful outcome with no recurrence of both the tumor and the endotheliitis for over 16 months.

Effectiveness of Topical Ganciclovir 2% Monotherapy Versus Combined Steroid Therapy in Cytomegalovirus Endotheliitis.

We aimed to report the clinical manifestations of cytomegalovirus (CMV) corneal endotheliitis and the results of long-term treatment with topical ganciclovir 2% with and without steroids. This retrospective, interventional study included 15 eyes of 13 patients diagnosed with CMV corneal endotheliitis by positive CMV DNA and treated with long-term topical ganciclovir 2% eye drops at a tertiary referral center and the median follow-up period was 17 months. Ocular manifestations included keratic precipitates (KPs) (100%), elevated IOP (93.3%), iritis (60%), corneal edema (60%), and moth-eaten iris atrophy (60%). After long-term treatment, corneal edema, iritis, and KPs significantly decreased (effect size: 72%, 76% and 70%, respectively; p = 0.024, p = 0.006 and p < 0.001, respectively). Both the logMAR acuity and IOP significantly improved (median logMAR was 0.52 before treatment and 0.22 after treatment; median IOP was 42 mmHg before treatment and 12 mmHg after treatment; p = 0.001 and p < 0.001, respectively). The ECD was maintained (effect size: 80%), and the percentage of hexagonal cell ratio of endothelial cells significantly improved after treatment (effect size: 82%; p = 0.035). Fewer anti-glaucoma medications were used in the non-steroid group (effect size: 79%; p = 0.034). Long-term maintenance treatment with topical ganciclovir 2% monotherapy not only provides effective therapy and reduces recurrence, but also decreases the high IOP related to the combination of steroids used.

Clinical Features of Glaucoma Associated with Cytomegalovirus Corneal Endotheliitis.

PurposeThe purpose of this study was to highlight the manifestations of glaucoma associated with cytomegalovirus (CMV) corneal endotheliitis.MethodsWe reviewed the 34 patients that met the diagnostic criteria for CMV endotheliitis in our hospital, with special attention to the glaucoma status, including onset of glaucoma, glaucoma in the fellow eye, visual field defects, intraocular pressure, and final outcomes.ResultsThirty-four eyes of 34 patients (mean age, 69.1 ± 13.1 years; 31 males [91.2%]) with CMV corneal endotheliitis were enrolled. Thirty-two eyes (94.1%) had a history of a glaucoma diagnosis, which had been treated for 10.0 ± 10.1 years. Glaucoma in the fellow eye was noted in 16 cases (47.1%) and a history of Posner-Schlossman syndrome was noted in 13 cases (38.2%). Visual fields measured using a Humphrey field analyzer were normal-to-early stage (MD>-6dB) in 16 eyes (47.1%) and middle-to-late stage (MD≤-6dB) in 18 eyes (52.9%). The intraocular pressure decreased from 22.4 ± 10.6 mmHg at the initial visit to 14.9 ± 7.9 mmHg after medical treatment, including 0.5% topical ganciclovir (GCV) with and without a systemic anti-CMV agent, corticosteroid eye drops, and an anti-glaucoma agent (p<0.01). During the follow-up period of 4.8 ± 3.0 years (range, 0.2–10 years), 16 eyes (47.1%) required glaucoma surgery, including filtering surgery (7 eyes) and trabeculotomy only (9 eyes).ConclusionOur case series showed that most of the patients with CMV corneal endotheliitis had glaucoma. Although medical therapy, including 0.5% topical GCV, had efficacy in lowering the intraocular pressure, one-half of the cases required glaucoma surgery. Therefore, ophthalmologists should strive to make an earlier diagnosis of CMV corneal endotheliitis by utilizing PCR testing of aqueous humor samples to prevent sight-threatening glaucomatous damage.

Clinical Metagenomic Next-Generation Sequencing for Diagnosis of Secondary Glaucoma in Patients With Cytomegalovirus-Induced Corneal Endotheliitis.

Glaucoma is the second leading cause of blindness globally. Growing scientific evidence indicated that inflammation of the trabecular meshwork induced by corneal endotheliitis could lead to secondary glaucoma. Cytomegalovirus (CMV) has been identified as the most common herpes virus in corneal endotheliitis patients. Early detection is critical in preventing endothelial cell loss, and patient management should vary based on different pathological factors. However, routine culture and real-time polymerase chain reaction (qPCR) have difficult in distinguishing whether CMV, Varicella Zoster Virus (VZV) or Herpes Simplex Virus (HSV) causes endothiliitis. This may result in inappropriate treatment, which may prolong or aggravate the status of disease. We compared the sensitivity and specificity of qPCR and Metagenomic Next-Generation Sequencing (mNGS) in the aqueous humor of patients with suspected CMV endotheliitis in this study. Our results showed that four out of 11 (36.4%) of our patients were positive for CMV by qPCR, whereas mNGS had a 100% detection rate of CMV. Our findings implied that mNGS could be a useful diagnostic tool for CMV-induced endotheliitis.

Cytomegalovirus as a cause of recurrent corneal endotheliitis in the Canadian population

ObjectifPrésenter les manifestations cliniques, la réponse au traitement antiviral et les résultats visuels à long terme de l'endothélite à cytomégalovirus (CMV) au sein d'une cohorte canadienne. NatureÉtude rétrospective d'une série de cas. ParticipantsUn total de 7 patients (9 yeux) atteints d'endothélite cornéenne ont été adressés à une clinique spécialisée dans le traitement des troubles de la cornée intégrée à un important établissement canadien. MéthodesOn a réalisé un examen rétrospectif de tous les patients qui avaient consulté un seul et même chirurgien spécialisé dans les troubles de la cornée en raison d'une endothélite cornéenne. Les patients ont subi une ponction de chambre antérieure et obtenu un résultat positif lors d'un test de dépistage (réaction en chaîne de la polymérase) du CMV. Tous les patients ont reçu le valganciclovir par voie orale pendant un minimum de 3 mois. Les principaux paramètres de mesure comprenaient l'acuité visuelle, la maîtrise de l'hypertension oculaire, la dépendance médicamenteuse et l’état de la cornée. RésultatsLa durée moyenne du suivi a été de 76,4 ± 11,8 mois. Seuls 2 patients présentaient une atteinte bilatérale. On compte 3 types de manifestations de l'endothélite touchant la cornée : les lésions linéaires, disciformes et circinées. La meilleure acuité visuelle corrigée est passée d'une moyenne de 0,48 ± 0,19 logMAR lors de la visite initiale à 0,24 ± 0,11 logMAR lors de la dernière visite de suivi. La pression intraoculaire, pour sa part, est passée d'un maximum de 35 ± 3,1 mm Hg à 14,2 ± 4,3 mm Hg. Le nombre d'antiglaucomateux a diminué, passant de 2,6 ± 0,45 collyres à 0,89 ± 0,29. On a dû procéder à une transplantation endothéliale dans 2 yeux. Le valganciclovir a été bien toléré par l'ensemble des patients; au moment de la dernière visite de suivi, l’état de tous les patients était stable sous l'effet de faibles doses de valganciclovir (dose moyenne hebdomadaire : 1395 mg). ConclusionsLe CMV est une cause peu fréquente, mais cliniquement significative, d'endothélite cornéenne et doit être pris en considération dans le diagnostic différentiel de l'endothélite cornéenne, même au sein d'une population immunocompétente. Nos résultats étayent ceux d’études antérieures selon lesquels le CMV réagit très bien au valganciclovir par voie orale et illustrent pour la première fois l'efficacité d'un traitement antiviral d'entretien faiblement dosé au long cours.

Clinical Findings of Specular Microscopy Images in Cytomegalovirus Corneal Endotheliitis.

The aim of this study is to evaluate the usefulness of specular microscopy as an alternative diagnostic tool for cytomegalovirus (CMV) corneal endotheliitis. A retrospective study. One hundred and four patients with clinical manifestations of infectious corneal endotheliitis, iridocyclitis, and retinitis were included in this study. The presence of CMV deoxyribonucleic acid (DNA) was confirmed by multiplex polymerase chain reaction (PCR). Viral load was measured using real-time PCR. Corneal endothelium was observed by specular microscopy. The medical records and clinical manifestations of the patients were retrospectively reviewed and linked with the PCR results. Seventeen of 104 cases were CMV endotheliitis and/or iridocyclitis and had no history of intraocular surgery or corneal transplantation. There was a negative correlation between viral load and corneal endothelial cell counts. In 14 of 17 cases, owl's eye cells were observed by specular microscopy. The corneal endothelial cell counts were significantly reduced in the cases in which owl's eye cells were observed. In CMV endotheliitis, owl's eye cells were observed by specular microscopy with high probability (82%). Corneal endothelial cells significantly decreased when owl's eye cells were observed by specular microscopy. Specular microscopy represents a useful noninvasive auxiliary tool for diagnosing and monitoring CMV corneal endotheliitis.

Antiviral cytotoxic T lymphocyte responses for long term prognosis of corneal infection by cytomegalovirus in immunocompetent subjects

Ocular cytomegalovirus (CMV) infections in immunocompetent individuals are rare, but its activation can cause chronic and relapsing inflammation in anterior segment of the eye resulting in loss of corneal clarity and glaucoma. Fifty five patients with anterior segment CMV infection were assessed for their clinical characteristics, and CMV corneal endotheliitis was found to cause significant loss of corneal endothelial cells. The disease duration with recurrences was significantly correlated with the maximum intraocular level of CMV DNA. To examine why CMV is activated in healthy immunocompetent individuals and causing corneal endothelial cell damage, assays of cytotoxic T cells (CTLs) which directly target infected corneal endothelial cells were performed for 9 HLA-matched CMV corneal endotheliitis patients (HLA-A*2402). When the cell loss was analyzed for associations with CTL responses, CMV-induced endothelial cell damage was mitigated by pp65-specific CTL induction. The recurrence-free time was also prolonged by pp65-specific CTL induction (hazard ratio (HR): 0.93, P = 0.01). In contrast, IE1-specific CTL was associated with endothelial cell damage and reduced the time for corneal transplantation (HR: 1.6, P = 0.003) and glaucoma surgery (HR: 1.5, P = 0.001). Collectively, induction of pp65-specific CTL was associated with improved visual prognosis. However, IE1-specific CTL without proper induction of pp65-specific CTL can cause pathological damage leading to the need of surgical interventions.

Coin-shaped corneal endothelial scar in herpes zoster ophthalmicus: a case report

BackgroundHerpes zoster ophthalmicus includes a wide spectrum of lesions at the ocular surface, including epithelial, stromal, endothelial keratitis, and uveitis. Thus far, the occurrence of corneal endothelial disorder in herpes zoster ophthalmicus and the causative virus have not been confirmed, and the differential diagnosis and establishment of therapeutic strategies are challenging. Corneal endothelial coin-shaped lesions are well known to occur in cytomegalovirus-related corneal endotheliitis but have not been reported in patients with herpes zoster ophthalmicus.Case presentationA 39-year-old Asian female was referred to our ophthalmology department with recurrent anterior uveitis accompanied by coin-shaped corneal endothelial scar-like lesions that appeared after right facial herpes zoster. Diffuse corneal stromal haziness was mostly limited in the anterior stroma. The coin-shaped corneal endothelial lesions were separate from stromal lesions and showed a high-reflective scar-like line in sections of anterior segment optical coherence tomography. Anterior uveitis recurred each time she discontinued oral antiviral drug treatment for 12 months after the first event, but was remitted by the maintenance medications of combined topical ganciclovir gel with oral valaciclovir, at a dose lower than the usual adult dose, for acute or recurrent zoster-associated anterior uveitis. Corneal endothelial function remained normal and corneal endothelial and stromal lesions were unchanged throughout the treatment and follow-up period.ConclusionsIn patients with a history of facial herpes zoster with coin-shaped corneal endothelial scar accompanying recurrent anterior uveitis, suspicion for active varicella-zoster virus is warranted, and prolonged intake of oral antiviral agents is required despite varicella-zoster virus DNA not being detected in aqueous humor.

A Fully Automated Segmentation and Morphometric Parameter Estimation System for Assessing Corneal Endothelial Cell Images

To develop a fully automated segmentation and morphometric parameter estimation system for assessing corneal endothelial cells from in vivo confocal microscopy images. Artificial intelligence (neural network) study. First, a fully automated deep learning system for assessing corneal endothelial cells was developed using the development set (from 99 subjects). Second, 184 images (from 97 subjects) were used to construct the testing set to evaluate the clinical validity and usefulness of the automated segmentation and morphometric system. Third, the automatically calculated endothelial cell density (ECD) values, Topcon's cell density, and manually calculated ECD were compared. After slit lamp examination, 88 healthy subjects, 2 Fuchs endothelial dystrophy patients, and 7 corneal endotheliitis patients were identified among the 97 subjects in the testing set. The automatedly estimated morphometric parameters for the testing set were an average number of 234 cells, an ECD of 2592 cells/mm2, a coefficient of variation in the cell area of 32.14%, and a percentage of hexagonal cells of 54.16%. Pearson's correlation coefficient between the automated ECD and Topcon's cell density and between the manually calculated ECD and Topcon's cell density was 0.932 (P < .01) and 0.818 (P < .01), respectively. The Bland-Altman plot of Topcon's cell density and the automated ECD yielded 95% limits of agreement between 271.94 and -572.46 (concordance correlation coefficient=0.9). A fully automated method for segmenting corneal endothelial cells and estimating morphometric parameters using in vivo confocal microscopy images is more efficient and accurate for assessing the normal corneal endothelium.