Herpetic Keratitis Research Articles

Feasibility assessment of infectious keratitis depicted on slit-lamp and smartphone photographs using deep learning

BackgroundThis study aims to investigate how infectious keratitis depicted on slit-lamp and smartphone photographs can be reliably assessed using deep learning. Materials and MethodsWe retrospectively collected a dataset consisting of 5,673 slit-lamp photographs and 400 smartphone photographs acquired on different subjects. Based on multiple clinical tests (e.g., cornea scraping), these photographs were diagnosed and classified into four categories, including normal (i.e., no keratitis), bacterial keratitis (BK), fungal keratitis (FK), and herpes simplex virus stromal keratitis (HSK). We preprocessed these slit-lamp images into two separate subgroups: (1) global images and (2) regional images. The cases in each group were randomly split into training, internal validation, and independent testing sets. Then, we implemented a deep learning network based on the InceptionV3 by fine-tuning its architecture and used the developed network to classify these slit-lamp images. Additionally, we investigated the performance of the InceptionV3 model in classifying infectious keratitis depicted on smartphone images. We, in particular, clarified whether the computer model trained on the global images outperformed the one trained on the regional images. The quadratic weighted kappa (QWK) and the receiver operating characteristic (ROC) analysis were used to assess the performance of the developed models. ResultsOur experiments on the independent testing sets showed that the developed models achieved the QWK of 0.9130 (95% CI: 88.99–93.61%) and 0.8872 (95% CI: 86.13–91.31%), and 0.5379 (95% CI, 48.89–58.69%) for the global images, the regional images, and the smartphone images, respectively. The area under the ROC curves (AUCs) were 0.9588 (95% CI: 94.28–97.48%), 0.9425 (95% CI: 92.35–96.15%), and 0.8529 (95% CI: 81.79–88.79%) for the same test sets, respectively. ConclusionThe deep learning solution demonstrated very promising performance in assessing infectious keratitis depicted on slit-lamp photographs and the images acquired by smartphones. In particular, the model trained on the global images outperformed that trained on the regional images.

Expert consensus on the identification, diagnosis, and treatment of neurotrophic keratopathy

BackgroundNeurotrophic keratopathy (NK) is a relatively uncommon, underdiagnosed degenerative corneal disease that is caused by damage to the ophthalmic branch of the trigeminal nerve by conditions such as herpes simplex or zoster keratitis, intracranial space-occupying lesions, diabetes, or neurosurgical procedures. Over time, epithelial breakdown, corneal ulceration, corneal melting (thinning), perforation, and loss of vision may occur. The best opportunity to reverse ocular surface damage is in the earliest stage of NK. However, patients typically experience few symptoms and diagnosis is often delayed. Increased awareness of the causes of NK, consensus on when and how to screen for NK, and recommendations for how to treat NK are needed.MethodsAn 11-member expert panel used a validated methodology (a RAND/UCLA modified Delphi panel) to develop consensus on when to screen for and how best to diagnose and treat NK. Clinicians reviewed literature on the diagnosis and management of NK then rated a detailed set of 735 scenarios. In 646 scenarios, panelists rated whether a test of corneal sensitivity was warranted; in 20 scenarios, they considered the adequacy of specific tests and examinations to diagnose and stage NK; and in 69 scenarios, they rated the appropriateness of treatments for NK. Panelist ratings were used to develop clinical recommendations.ResultsThere was agreement on 94% of scenarios. Based on this consensus, we present distinct circumstances when we strongly recommend or may consider a test for corneal sensitivity. We also present recommendations on the diagnostic tests to be performed in patients in whom NK is suspected and treatment options for NK.ConclusionsThese expert recommendations should be validated with clinical data. The recommendations represent the consensus of experts, are informed by published literature and experience, and may improve outcomes by helping improve diagnosis and treatment of patients with NK.

NSC23766 and Ehop016 Suppress Herpes Simplex Virus-1 Replication by Inhibiting Rac1 Activity

Herpes simplex virus-1 (HSV-1) infection of the eyes leads to herpes simplex virus keratitis (HSK), the main cause of infectious blindness in the world. As the current therapeutics for HSV-1 infection are rather limited and prolonged use of acyclovir (ACV)/ganciclovir (GCV) and in immunocompromised patients lead to the rise of drug resistant mutants, it underlines the urgent need for new antiviral agents with distinct mechanisms. Our study attempted to establish ras-related C3 botulinum toxin substrate 1 (Rac1) as a new therapeutic target for HSV-1 infection by using Rac1-specific inhibitors to evaluate the in vitro inhibition of virus growth. Our results showed that increased Rac1 activity facilitated HSV-1 replication and inhibition of Rac1 activity by NSC23766 and Ehop016 significantly reduced HSV-1 replication. Thus, we identified NSC23766 and Ehop016 as possessing potent anti-HSV-1 activities by suppressing the Rac1 activity, suggesting that Rac1 is a potential target for treating HSV-1-related diseases.

Harringtonine Inhibits Herpes Simplex Virus Type 1 Infection by Reducing Herpes Virus Entry Mediator Expression.

Herpes simplex virus type 1 (HSV-1) infection induces various clinical disorders, such as herpes simplex encephalitis (HSE), herpes simplex keratitis (HSK), and genital herpes. In clinical intervention, acyclovir (ACV) is the major therapeutic drug used to suppress HSV-1; however, ACV-resistant strains have gradually increased. In the present study, harringtonine (HT) significantly inhibited infection of HSV-1 as well as two ACV-resistant strains, including HSV-1 blue and HSV-1 153. Time-of-drug addition assay further revealed that HT mainly reduced the early stage of HSV-1 infection. We also demonstrated that HT mainly affected herpes virus entry mediator (HVEM) expression as shown by qPCR, Western Blot, and Immunofluorescence. Collectively, HT showed antiviral activity against HSV-1 and ACV-resistant strains by targeting HVEM and could be a promising therapeutic candidate for mitigating HSV-1-induced-pathogenesis.

Conjunctival herpetic ulcer in an immunosuppressed patient with birdshot chorioretinopathy

Introduction: Herpes Simplex Virus (HSV) is a human herpesvirus responsible for systemic infections. Ocular involvement spans all ocular tissues. Corneal lesions, such as dendritic or geographic ulcers, are frequently found in HSV keratitis while conjunctival lesions have been described as infrequent.
 Clinical case: A 62-year-old man diagnosed with Birdshot chorioretinopathy presented a stye in his eyelid that was treated with oxytetracycline-hydrocortisone ointment. One week later he returned presenting several small dendritic corneal ulcers in both eyes and a conjunctival ulcer in one of them. All lesions healed completely after treatment with topical acyclovir ophthalmic ointment at 3%.
 Conclusions: We should pay attention to the conjunctiva and not merely focus on the cornea when examining patients with herpetic eye disease, especially if being treated with inmunosupressors.

Fermented pomegranate extracts protect against oxidative stress and aging of skin.

Punica granatum (pomegranate) potentially ameliorates skin inflammation and pain, including herpetic stromal keratitis. Fermentation is a biotechnological technique that may naturally induce health benefits by producing antioxidants. However, the anti-aging effect of fermented pomegranate extracts (FPE) on the skin is still unclear. This investigation evaluates the effects of fermented pomegranate as a functional supplement (FPE drink, FPE-D) and a cosmetic ingredient (FPE serum, FPE-S) in vitro and in vivo. The effects of FPE products for anti-oxidation, anti-tyrosinase, anti-inflammation, and anti-aging were examined. Forty subjects were randomly allocated to FPE-D or placebo drink groups (50ml of a FPE-D /placebo drink daily for 8weeks for each subject), and another 40subjects were recruited to FPE-S or placebo serum groups (about 3ml of a FPE-S /placebo serum daily and nightly/daily for 4weeks for each subject) in a double-blind study. The effects of FPE products on the DPPH, ABTS+ , and NO· free radical scavenging activities, their inhibiting of tyrosinase activity and their enhancement of the skin health of healthy subjects, were investigated. FPE-D improved the moisture, brightness, elasticity, and collagen density of the skin of most subjects at 8weeks relative to the baseline without treatment (p<0.05). After 4weeks of FPE-S serum consumption, the moisture, brightness, elasticity, spots, UV spots, and collagen density of skin were slightly better than those at week 0 (p<0.05). The daily consumption of fermented pomegranate extracts can protect the skin against oxidative stress and slow skin aging.

Herpes Simplex Virus Keratitis Reactivation after SARS-CoV-2 BNT162b2 mRNA Vaccination: A Report of Two Cases

ABSTRACT Purpose To report two cases of herpes simplex virus keratitis reactivation following Pfizer-BioNTech COVID-19 (BNT162b2) mRNA vaccination. Methods Two patients (one male, age 42 years, and one female, age 29 years) who are known to have herpetic keratitis presented to our emergency room in a time frame between 4 days and 4 weeks of receiving the vaccine. One patient presented with necrotizing stromal keratitis; the other presented with endotheliitis and epithelial keratitis. PCR for herpes simplex virus (HSV) was obtained from the two patients, and all cases received systemic acyclovir. Results PCR for HSV came positive in both cases. Patients responded well to the provided treatment. Conclusion Ocular herpetic infection may be activated by COVID-19 (BNT162b2) mRNA vaccine. Treating physician should be alert to such associations, and patients should be followed closely. No direct causality has been proven, but further reporting and investigating similar conditions is recommended.

Rational Design of Live-Attenuated Vaccines against Herpes Simplex Viruses.

Diseases caused by human herpes simplex virus types 1 and 2 (HSV-1 and HSV-2) affect millions of people worldwide and range from fatal encephalitis in neonates and herpes keratitis to orofacial and genital herpes, among other manifestations. The viruses can be shed efficiently by asymptomatic carriers, causing increased rates of infection. Viral transmission occurs through direct contact of mucosal surfaces followed by initial replication of the incoming virus in skin tissues. Subsequently, the viruses infect sensory neurons in the trigeminal and lumbosacral dorsal root ganglia, where they are primarily maintained in a transcriptionally repressed state termed “latency”, which persists for the lifetime of the host. HSV DNA has also been detected in other sympathetic ganglia. Periodically, latent viruses can reactivate, causing ulcerative and often painful lesions primarily at the site of primary infection and proximal sites. In the United States, recurrent genital herpes alone accounts for more than a billion dollars in direct medical costs per year, while there are much higher costs associated with the socio-economic aspects of diseased patients, such as loss of productivity due to mental anguish. Currently, there are no effective FDA-approved vaccines for either prophylactic or therapeutic treatment of human herpes simplex infections, while several recent clinical trials have failed to achieve their endpoint goals. Historically, live-attenuated vaccines have successfully combated viral diseases, including polio, influenza, measles, and smallpox. Vaccines aimed to protect against the devastation of smallpox led to the most significant achievement in medical history: the eradication of human disease by vaccination. Recently, novel approaches toward developing safe and effective live-attenuated vaccines have demonstrated high efficacy in various preclinical models of herpetic disease. This next generation of live-attenuated vaccines has been tailored to minimize vaccine-associated side effects and promote effective and long-lasting immune responses. The ultimate goal is to prevent or reduce primary infections (prophylactic vaccines) or reduce the frequency and severity of disease associated with reactivation events (therapeutic vaccines). These vaccines’ “rational” design is based on our current understanding of the immunopathogenesis of herpesviral infections that guide the development of vaccines that generate robust and protective immune responses. This review covers recent advances in the development of herpes simplex vaccines and the current state of ongoing clinical trials in pursuit of an effective vaccine against herpes simplex virus infections and associated diseases.

Herpetic endotheliitis following an uncomplicated cataract surgery

Introduction: Herpetic endotheliitis after cataract surgery is a rare complication, and it is more likely linked with previous ocular herpetic infection. Case Report: In the current case, the patient of this study is a 66-year-old woman without a personal history of herpes simplex keratitis (HSK) who underwent an uneventful phacoemulsification in her left eye. For the next two weeks, corneal endotheliitis appeared in the same eye, and then the initial diagnosis of HSK was made clinically. The patient was treated with systemic and topical antiviral therapy associated with an intensive topical corticosteroid. In four weeks, a complete resolution of the corneal edema was noticed and the visual acuity was improved (6/9). Conclusion: The occurrence of corneal edema after cataract surgery could reveal a herpetic endotheliitis, although early diagnosis and early treatment with strict monitoring are the keys to successful control of this affection.

Clinical outcomes of herpes simplex keratitis: Two-year experience from a quaternary eye care centre in Sydney, Australia.

To report anti-viral therapy and outcomes for patients with herpes simplex keratitis (HSK) in a quaternary centre in Sydney, Australia. A retrospective case review of patients who received anti-viral medications for any form of HSK was conducted. Cases were identified from pathology results, pharmacy records and hospital coding data from 2012 to 2013. Clinical details including initial anti-viral treatment and outcome were collated from the medical records. Outcome was determined from when initial anti-viral treatment was stopped or changed, and classified as either clinically resolved, partially resolved or worsened for therapeutic indication; or as either success or failure for prophylaxis. Anti-viral therapy was given for therapeutic and prophylactic indications at presentation in 252 (85%) and 44 patients (15%), respectively. Topical aciclovir five times daily and valaciclovir in doses ranging from 500mg to 1g, one to three times daily were the preferred anti-viral therapies. One hundred and fourteen patients (n=114/296, 38.5%) also received topical corticosteroids. An outcome was determined for 210/296 (71%) patients. For therapeutic indication, half of the patients (90/174) partially resolved within 8days, with best outcomes achieved for endothelial HSK (8/11, 73%) and keratouveitis (21/36, 58%). Adverse events, observed in 20% (35/174) of patients, included corneal perforation (n=8) and secondary bacterial keratitis (n=6). Prophylaxis with antiviral therapy was successful in two-thirds of patients after 6months. Clinical and visual outcomes varied with the type of HSK and prescribed therapies. Diverse initial anti-viral therapies were identified; standardising them may improve outcomes.

Dendritic epithelial keratitis in primary herpes simplex infection.

Abstract A 76-year-old man with a 3-day history of redness, itchiness and blurred vision in the right eye. Ocular examination of the right eye showed dendritic ulcers, limited to epithelium, on the surface of the cornea. After staining with fluorescein dye, the right eye revealed multiple small branching epithelial dendrites with terminal bulbs on the surface of the cornea. Herpes simplex keratitis of right eye was diagnosed.

HERPES SIMPLEX VIRUS (HSV) KERATITIS BILATERAL WITH FILAMENTOUS

Introduction : Herpetic keratitis is caused by herpes simplex virus and is a common cause of corneal blindness. Generally herpes simplex keratitis is a unilateral disease, but bilateral disease has been reported in 1,3 % to 10,9 % of patients. Filamentous keratitis most often caused by dry eye, especially aqueous tear-deficient dry eye. Objective: To report a case of bilateral herpes simplex virus keratitis bilateral with filamentous. Method: A 45 years old man was admitted to Dr. M. Djamil Hospital Padang presented with glare and blurred on both eyes since 1 week ago. VA RE is 6/30, VA LE is 6/60. On ophthalmology examination were conjunctival and ciliary injection. On the cornea of both of eyes, found infiltrate numular shaped almost all of layer of the cornea. Cornea sensitivity was decreased on both eyes. Patient diagnosed by numularis keratitis of both eyes and therapy is oral and topical acyclovir. After 2 weeks therapy, we found filamentous on left eye. Debridement of filament was performed and the therapy was continued. Result: There are improvement of visual acuity and clinical feature. VA RE 6/15, LE 6/40. Subjectively, patient feel comfort. The sign of glare and photophobia are decrease. Density of infiltrate was decrease and no filamentous was found.

This issue of ACTA

This issue of ACTA

Visual outcomes of herpes simplex keratitis in children age 6 years and younger

Herpes simplex keratitis is a leading cause of pediatric visual loss worldwide. This study explored the effects of delay in treatment and subsequent decreased vision from corneal scarring and amblyopia.

Preparation and optimization formulation of zedoary turmeric oil nanoemulsion based thermo-sensitive gel for improved application in ophthalmology

The purpose of the current study was to design and develop a dosage form of zedoary turmeric oil nanoemulsion based thermo-sensitive gel (ZTO-NETG), improved the solubility and stability of zedoary turmeric oil and provided an ocular delivery strategy for the treatment of Herpes Simplex Keratitis. ZTO-NETG was prepared by phase inversion method and pseudo-ternary phase diagram, response surface experiment design was employed for the optimization of formulation. Physicochemical properties, in vitro drug release, stability studies stability and prediction of the validity by the classical thermostatic method of the optimized ZTO-NETG formulation were investigated. Moreover, modified Draize tests was applied to evaluate the ZTO-NETG formulation ocular irritation. The optimized ZTO-NETG showed the size of 98.52 nm, polydispersity index of 0.180, Zeta potential of - 4.12 mV and the drug content of Germacrone 97.8% and Furanodiene 102.3%. Viscosity and rheology demonstrated that ZTO-NETG had thinning effect, invitro release study showed that the release kinetics of the optimized gel conformed to zero-order drug release. Ocular irritation tests indicated that the eyes could tolerate the optimized ZTO-NETG. The result of the stability test was proved that the optimized gel had good physical stability, and the validity period of ZTO-NETG was 4 months. In conclusion, this thermo-sensitive gel formulation strategy could be used as a viable option for ocular administration of zedoary turmeric oil to treat Herpes Simplex Keratitis.

Severe Ocular Graft-Versus-Host Disease Successfully Treated with Amniotic Membrane Transplantation - Case Series

Ocular graft-versus-host disease (GVHD) has the potential to lead to serious vision impairment, restriction of daily activities and deterioration of quality of life of patients after allogeneic stem cell transplantation (allo-SCT). Amniotic membrane transplantation (AMT) is an established technique in the treatment of various diseases of the ocular surface. This method could provide new options in the management of otherwise disabling severe ocular GVHD.We report a case-series of four patients with severe ocular GVHD refractory to standard local and systemic therapy, successfully treated with AMT. First patient was a 26-year old male who underwent a related allo-SCT for lymphoblastic transformation of chronic myeloid leukemia (CML) and received three donor lymphocytes infusions (DLI) due to molecular relapse. Six months later he developed severe GVHD of the mouth and eye that gradually deteriorated, despite corticosteroid treatment and topical therapy, and finally led to corneal perforation. In this case AMT was used to successfully seal the corneal perforation and to avoid keratoplasty. Moreover, AMT led to a durable clinical improvement continuing for four years after the treatment without the need for systemic immunosuppression. The second patient was a 25-year old male, transplanted from an unrelated donor for a CML refractory to tyrosine kinase inhibitors, who received one DLI for mixed chimerism and consequently developed GVHD of the skin, liver, lungs and eyes. Ocular GVHD progressed despite local and triple systemic immunosuppressive treatment. In this case AMT was applied before severe corneal ulcerations developed and led to full clinical recovery. The third patient was a 32-year old female who underwent an unrelated myeloablative allo-SCT for myelofibrosis, complicated with acute liver GVHD and slow immune reconstitution. At day +150 she developed a disabling herpes keratitis and stomatitis which led to prolonged hospitalization and slow recovery. At day +280 her vision deteriorated again, this time with signs of severe ocular GVHD. We feared herpes reactivation and hesitated from increasing immunosuppression. With this rationale we decided to perform AMT which again led to significant clinical improvement. Finally, our fourth patient underwent unrelated allo-SCT in the age of 22 for high risk myelodysplastic syndrome complicated with toxic epidermal necrolysis (TEN) of the skin, mucosa and eye. In this case chronic GVHD of the eye developed eight months later and gradually progressed, partly due to patient's non-compliance with treatment. This time AMT was applied on two consecutive occasions resulting in a similarly impressive clinical effect. The latter two patients also had marked corneal vascularization possibly due to the preceding involvement of the eye with viral infection and TEN. This was efficiently treated with additional subconjunctival anti-VEGF injections. With a median follow-up of 15 months, all four patients remained clinically stable without recurrence of severe ocular GVHD.Amniotic membrane is rich in cytokines, growth factors and protease inhibitors and serves as a biological bandage that suppresses inflammation and promotes epithelialization. In our experience, beside acute healing of corneal ulcerations in severe ocular GVHD and preventing perforation, it has a durable effect and prevents GVHD recurrence. Moreover, with the use of AMT we can avoid systemic immunosuppression and decrease both the risk of infectious complications and recurrence of the primary malignancy in allo-SCT patients. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Amniotic membrane transplantation for infectious keratitis: a systematic review and meta-analysis

Infectious keratitis (IK) is the 5th leading cause of blindness globally. Broad-spectrum topical antimicrobial treatment is the current mainstay of treatment for IK, though adjuvant treatment or surgeries are often required in refractory cases of IK. This systematic review aimed to examine the effectiveness and safety of adjuvant amniotic membrane transplantation (AMT) for treating IK. Electronic databases, including MEDLINE, EMBASE and Cochrane Central, were searched for relevant articles. All clinical studies, including randomized controlled trials (RCTs), non-randomized controlled studies and case series (n > 5), were included. Primary outcome measure was time to complete corneal healing and secondary outcome measures included corrected-distance-visual-acuity (CDVA), uncorrected-distance-visual-acuity (UDVA), corneal vascularization and adverse events. A total of twenty-eight studies (including four RCTs) with 861 eyes were included. When compared to standard antimicrobial treatment alone, adjuvant AMT resulted in shorter mean time to complete corneal healing (− 4.08 days; 95% CI − 6.27 to − 1.88; p < 0.001) and better UDVA (− 0.26 logMAR; − 0.50 to − 0.02; p = 0.04) at 1 month follow-up in moderate-to-severe bacterial and fungal keratitis, with no significant difference in the risk of adverse events (risk ratio 0.80; 0.46–1.38; p = 0.42). One RCT demonstrated that adjuvant AMT resulted in better CDVA and less corneal vascularization at 6 months follow-up (both p < 0.001). None of the RCTs examined the use of adjuvant AMT in herpetic or Acanthamoeba keratitis, though the benefit was supported by a number of case series. In conclusion, AMT serves as a useful adjuvant therapy in improving corneal healing and visual outcome in bacterial and fungal keratitis (low-quality evidence). Further adequately powered, high-quality RCTs are required to ascertain its therapeutic potential, particularly for herpetic and Acanthamoeba keratitis. Future standardization of the core outcome set in IK-related trials would be invaluable.

A Retrospective Study of Herpetic Keratitis in Patients with Keratoconus after Crosslinking Surgery.

Background: The aim of this study was to perform a retrospective analysis of patients who underwent cross-linking for keratoconus, in the Department of Ophthalmology of the Medical University of Silesia in Katowice, between 2011 and 2020, regarding the occurrence of herpetic keratitis after the procedure. Methods: We analyzed the medical history of 543 patients who underwent cross-linking surgery. Results: In the analyzed group, there were nine cases of herpetic keratitis (six men and three women), aged from 16 to 40 years (mean 26.2 years). The mean follow-up period was 49.3 months (16–82 months). The average time from surgery to the manifestation of the first symptoms of keratitis was 4.3 days (2–6 days). In two cases, iritis was observed, and in one of them, iritis was the first symptom. After systemic and topical administration of acyclovir, ulceration healed in all patients. Corneal healing time ranged from 10 days to 3 weeks (average 13.7 days). In one patient, a recurrence of the inflammation was observed after 8 months. Conclusion: Patients should be carefully observed in the early post-CXL period. Herpetic keratitis could be induced by CXL even in patients with no history of herpetic disease.

Herpes simplex virus PCR in 2230 explanted corneal buttons.

To determine herpes simplex virus (HSV) DNA prevalence and mean cycle threshold of polymerase chain reaction (PCR) in corneal tissue of patients with penetrating keratoplasty (PKP), with (HSK+) and without (HSK-) previous clinical herpetic keratitis history. Retrospective review of recipient corneal buttons which were explanted through PKP between March 2010 and September 2018 at the Department of Ophthalmology, Saarland University Medical Center in Homburg/Saar, Germany. Corneal tissue samples were analysed by real-time PCR for the presence of HSV DNA. For each subject, clinical data, including patients' demographics and clinical diagnoses, were collected. In total, 2230 corneal samples (age at the time of the surgery 57.3 ± 19.2 years) of 1860 patients were analysed. HSV PCR was positive in 137 (6.1%) corneal samples, with a 30.57 ± 6.01 (range 14-39) mean cycle threshold (Ct) value. Two hundred ninety-eight (13.4%) corneas of 266 patients were clinically HSK+, and 1932 (86.6%) corneas of 1600 patients were clinically HSK-. HSV DNA was detected significantly more frequently (p < 0.0001) in HSK+ corneal samples (108 corneal samples; 36.2%), than in HSK- corneal samples (29 corneal samples; 1.5%). Ct value was significantly lower in HSK+ than in HSK- corneal samples (29.8 ± 5.8 versus 32.6 ± 5.9; p = 0.008). Our data demonstrate that a positive clinical history of HSK is related to HSV PCR positivity in about every 2.8th patient. In addition, about every 66th explanted corneal tissue is HSV PCR-positive despite the lack of clinical suspicion. These patients may need additional local/systemic antiviral treatment to avoid newly acquired HSK following penetrating keratoplasty.

Ultrastructural Alterations of Grafted Corneal Buttons: The Anatomic Basis for Stromal Peeling Along a Natural Plane of Separation

To examine the ultrastructure of the natural plane of separation in grafted corneas and evaluate the outcomes of stromal peeling. Interventional case series. In this multicenter study, stromal peeling was attempted in 96 consecutive eyes with unsatisfactory vision following penetrating keratoplasty (PK) for keratoconus (n=79), herpetic keratitis (n=11), and granular dystrophy (n=6). Stromal exchange was performed by (1) 9 mm partial-thickness trephination; (2) creation of a corneal flap across the PK wound; (3) opening of the stromal component of the PK wound until a smooth, translucent natural plane was identified; (4) severing the attachment of the PK scar; (5) stromal peeling along the identified plane; and (6) suturing of donor lamella. Grafted corneas from cases that mandated conversion to PK were processed for transmission electron microscopy. The natural plane of separation was identified in all cases. Stromal exchange was successfully completed in 84 cases (87.5%). Snellen visual acuity ≥20/40 and ≥20/25 was reached in 93% and 72% of cases at 3 years (n=49) and 86% and 62% at 4 years (n=21) postoperatively. Mean endothelial cell loss at 1 year was 6.6% ± 9.5%. Stromal peeling occurred along a plane lined with a continuous layer of keratocytes separating pre-Descemet membrane (DM) stroma, DM, and endothelium from the anterior stroma. Pre-DM stroma was made of poorly organized lamellae containing widely spaced, randomly arranged collagen fibrils. Ultrastructural alterations in the stromal microarchitecture of grafted corneas provide evidence of a natural plane of separation identified intraoperatively. Stromal peeling can be successfully performed in post-PK eyes with various stromal pathology.