Extracellular matrix changes in corneal opacification vary depending on etiology.

Purpose: The purpose of this study is to examine the expression of tenascin-C and matrilin-2 in three different disorders, which frequently require corneal transplantation. These pathological conditions include bullous keratopathy (BK), Fuchs' endothelial corneal dystrophy (FECD), and corneal scarring in herpetic keratitis. Methods: Histological sections of corneal buttons removed during keratoplasty were analyzed in BK (n = 20), FECD (n = 9), herpetic keratitis (n = 12), and cadaveric control (n = 10) groups with light microscopy following chromogenic immunohistochemistry. The sections were evaluated by three investigators, and semiquantitative scoring (0 to 3+) was applied according to standardized methods at 400X magnification. Each layer of the cornea was investigated; moreover, the stroma was subdivided into subepithelial, middle, and pre-Descemet's membrane areas for more detailed analysis. Results: Excessive epithelial and stromal expression of tenascin-C was identified in all investigated conditions; the results were most pronounced in the pre-Descemet's membrane. Regarding matrilin-2, when examined in BK, there was increased labeling intensity in the epithelium (p<0.001) and stromal layers (p<0.05), and a decrease in the endothelium (p<0.001). In the other investigated conditions, only a low degree of stromal localization (p<0.05) of matrilin-2 was detected. Conclusions: The expression of tenascin-C and matrilin-2 differs when examined in various corneal pathologies resulting in opacification. Both molecules seem to be involved in regeneration and wound healing of the corneal matrix in these diseases.

Herpes Simplex Virus Keratitis in a University Tertiary Referral Centre - Clinical Features and Surgical Approaches.

PURPOSE: To assess prevalence, clinical manifestations, required keratoplasties, follow-up, and outcome in patients with Herpes Simplex Virus Keratitis (HSK) attending a University Tertiary Referral Center. DESIGN: Retrospective (12 years), descriptive, observational study. METHODS: A total of 817 eyes with clinical diagnosis of HSK from 779 patients were classified by the type of presentation. We gathered data on the visual acuity, refraction, IOP, and required surgical procedures. RESULTS: Stromal involvement including scars represented the most common diagnosis in our department and the main indication of penetrating keratoplasty (PKP). Epithelial keratitis (16%) presented with the best visual acuity at the first visit. Necrotizing keratitis represented 17% of the patients, 78% of whom required PKP; this group also had the worst visual acuity at first examination and was the main indication for emergency PKP. Among all eyes, 288 (35%) required PKP. A total of 230 (28%) PKPs were elective procedures and 58 (7%) PKPs were performed as emergency procedures. Two patients with quiet endothelial decompensations after recurrent HSV endotheliitis were treated with DMEK and had good visual outcomes without HSV recurrence at last follow-up. CONCLUSIONS: HSK is a prevalent disease with severe consequences when not treated appropriately and on time. Even when making an accurate diagnosis, the disease can be extremely aggressive, with all the implications it brings to the patients and health system. Elective PKP had better outcomes in terms of visual acuity and clear graft percentage compared to emergency PKP.

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.

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.

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.

Surgical management of herpetic keratitis.

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

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.

[Lamellar minikeratoplasty for recurrent herpes keratitis in the late post-LASIK period].

The article presents a case report of sutureless lamellar minikeratoplasty for progressive corneal ulceration associated with herpes simplex infection in the late period after LASIK.

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.

[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.

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.

Morphometric analysis of postoperative corneal neovascularization after high-risk keratoplasty: herpetic versus non-herpetic disease.

BACKGROUND: Postoperative complications after high-risk corneal grafting are decisively associated with corneal neovascularization (CNV). This study aimed to identify the incidence, extent, speed, localization, and influence of surgery-related factors on CNV after high-risk penetrating keratoplasty (PK) and to evaluate the effect of removing the angiogenic stimulus, i.e., residual components of herpes simplex virus (HSV) on postkeratoplasty CNV in patients with herpetic stromal keratitis (HSK). METHODS: All primary high-risk PK performed for HSK and non-herpetic keratitis (controls) between 1 January 1998 and 31 December 2003 at our department with available standardized corneal photographs taken preoperatively as well as 6 weeks, 3, 6 and 12 months postoperatively were evaluated (n (herpes) = 19, n (controls) = 5 patients). Maximal extension of CNV, limbus suture distance (LSD), limbus graft distance (LGD) and graft size in digitalized pictures were measured in each of the 16 sectors of the cornea at every visit. RESULTS: One hundred percent of the prevascularized corneas (n = 24) showed further CNV outgrowth within 1 year after keratoplasty, while 58 % of these patients featured high-grade CNV reaching the host-graft junction or invading the donor tissue. Overall, CNV outgrowth was fastest during the first 6 weeks after PK, with a mean speed of 48 µm/week. Mean CNV growth speed within 6 months post-PK was significantly lower in the herpes group (13 µm/week) than in the non-herpes group (25 µm/week, p = 0.017). Corneal location around the 12 o'clock position showed the most intense vessel outgrowth, which proved to be an independent risk factor for high-grade CNV (p = 0.025). Inverse correlation was evident between CNV growth speed and LSD (p = 0.032). CONCLUSIONS: Additional intense CNV outgrowth is a common phenomenon after high-risk keratoplasty, strongly marked in the early postoperative period. The removal of residual HSV components representing a potential angiogenic stimulus leads to a reduction in corneal angiogenesis not in the short term, but in the long term after PK in patients with HSK. In addition to preferable atraumatic operation techniques, modern antiviral prophylaxis and anti-angiogenic therapy should be applied early, possibly even prior to transplantation. Short LSD seems to be an intraoperative adjustable risk factor for CNV in high-risk setting. Attention should also be paid to the superior site around the 12 o'clock position.

Therapeutic effect of deep anterior lamellar keratoplasty for active or quiescent herpetic stromal keratitis.

PURPOSE: To evaluate the therapeutic effect of deep anterior lamellar keratoplasty (DALK) in patients with herpetic stromal keratitis (HSK). METHODS: Forty-three eyes belonging to 42 patients with HSK, including 22 eyes in the active phase and 21 eyes in the quiescent phase, underwent DALK at the Shandong Eye Institute from January 2006 to December 2009. All patients with active disease had received intravenous acyclovir and amniotic membrane implants prior to DALK. Herpes simplex virus type 1 (HSV-1) antigens from excised corneal buttons were detected by immunohistochemistry. RESULTS: The follow-up ranged from 1 to 4 years (mean, 29.1 months). Graft rejection occurred in one eye (2.3%) and was reversed. Among the other 42 survived grafts (97.7%), 37 remained clear at the last visit. The best spectacle-corrected visual acuity was 20/200 or better in 95.2% of eyes and 20/40 or better in 38.1% of eyes. Six eyes (14.0%) developed recurrent HSK, one of which received a second keratoplasty due to ineffective antiviral medication. There were no significant differences in endothelial cell density between 6 months and 12 months after the surgery. By immunohistochemistry, HSV-1 antigens were observed in the stroma of 18 of 32 corneal buttons. CONCLUSIONS: DALK can not only remove the corneal lesions of HSK but also reduce latent or persistent viral loads in the cornea. In eyes with active or quiescent HSK but otherwise healthy endothelia, DALK seems to be safe and promising for its favorable visual outcome, graft survival rate, and low endothelial cell loss.

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.

[Amniotic membrane transplantation in herpetic corneal infections]. / Amnionmembrantransplantation bei herpetischen Hornhautinfektionen.

Severe infectious corneal ulceration such as herpetic stromal keratitis commonly causes loss of vision and may lead to blindness. Treatment depending on the underlying disease includes antimicrobial medication and the development of surgical strategies to restore the integrity of the corneal ocular surface. Ulcerative herpetic stromal keratitis and/or neurotrophic keratopathy with the risk of corneal perforation are still clinically challenging conditions in ophthalmic surgery of the ocular surface. Since the introduction of newly developed preservation methods, amniotic membrane (AM) functioning as a basement membrane substitute has gained widespread popularity in ocular surface reconstruction. Various ways of clinical application such as the use of AM as a graft, patch or culture substrate and carrier system to expand ocular surface epithelia have been recently reported. In this article, the basis and clinical application of amniotic membrane transplantation for the management of corneal infections with Herpes simplex and Herpes zoster virus are reviewed.

[Penetrating keratoplasty in corneal infections with herpes simplex virus and varicella zoster virus]. / Perforierende Keratoplastik bei Hornhautinfektionen durch Herpes-simplex-Virus und Varizella-zoster-Virus.

Penetrating keratoplasties due to herpetic corneal scars are more often performed compared to persisting Varicella zoster virus infections, which are quite seldom. Penetrating keratoplasties in herpetic corneas are risk keratoplasties due to the vascularisation and the risk of recurrent virus replication. The prognosis in these corneal transplantations has been improved in recent years due to better postoperative medical treatment with virustatics and systemic immunosuppression. Indications for and treatment following penetrating keratoplasty in herpetic eyes are the topics of this review.

Corneal Graft Success Rates in HSV Keratitis: A Systematic Review.

Herpes Simplex Virus (HSV) has worldwide prevalence. The primary objective of this systematic review was to compare penetrating keratoplasty (PK) and deep anterior lamellar keratoplasty (DALK) regarding the efficacy and complications of the treatment of corneal scarring caused by herpes simplex keratitis. Out of the 469 articles identified during the combined search of the literature based on the PubMed and Cochrane libraries, 10 retrospective and 2 prospective studies published from January 2010 to December 2019 were included. The study outcomes indicated that both surgical approaches resulted in a comparable improvement of visual acuity (VA). However, DALK demonstrated fewer complications in the majority of studies. Higher graft survival rates were associated with higher acyclovir (ACV) doses (above 800 mg/day), topical steroid and antibiotic drops. In conclusion, in terms of postoperative VA, both PK and DALK demonstrate comparable efficacy. However, DALK, which is applied in less severe HSK cases, is associated with fewer complications and better graft survival rates. High dosages of ACV, topical steroids and antibiotics contribute significantly to improved postoperative outcomes.