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Purpose: To report the outcomes of initial high-dose and extended taper of antiviral and steroid prophylaxis for the treatment of eyes with high-risk vascularized herpetic corneal scars that underwent 2-piece mushroom keratoplasty (MK)., Design: Prospective interventional case series., Methods: In this single-center study, 52 consecutive eyes with vascularized (≥2 quadrants) herpetic corneal scars underwent 2-piece microkeratome-assisted MK. Initial high-dose and extended taper of combined oral and topical antiviral and steroid prophylaxis was administered. Outcome measures were best spectacle-corrected visual acuity (BSCVA), refractive astigmatism (RA), endothelial cell density, immunologic rejection, herpetic recurrence, and graft failure rates., Results: Excluding patients with vision-impairing comorbidities, baseline BSCVA (1.73 ± 0.67 logMAR) significantly improved annually during the first 2 years (P < .001, P = .016), reaching 0.17 ± 0.18 logMAR at year 2, and remaining stable up to 10 years (P = .662). At 2 years, 86% of eyes saw ≥20/40, 55% saw ≥20/25, and 18% saw ≥20/20 Snellen BSCVA. RA exceeded 4.5 diopters in 7% of cases after wound revision for high-degree astigmatism in 7 cases. Endothelial cell loss was 40.9% at 1 year with an annual decline of 3.1% over 10 years. The 10-year cumulative risk for immunologic rejection, herpetic recurrence, and graft failure was 9.7%, 7.8%, and 7.6%, respectively., Conclusions: Initial high dose and extended taper of antiviral and steroid prophylaxis for MK in high-risk, vascularized herpetic corneal scars achieves clinical outcomes that remain stable for up to 10 years after surgery with minimal risk of immunologic rejection, herpetic recurrence and graft failure., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Purpose: To report the clinical outcome and postoperative course of Descemet membrane endothelial keratoplasty (DMEK) in irreversible corneal edema due to herpes simplex virus (HSV) endotheliitis., Methods: This is a retrospective, noncomparative, interventional case series. Nineteen eyes of 19 patients underwent standard DMEK combined with cataract surgery (triple DMEK) between May 2016 and April 2018. All patients received perioperative oral acyclovir (ACV) and prednisolone. Patients were followed up on day 1, on day 7, at 1 month, and then at 3 monthly intervals. Preoperative and postoperative best spectacle-corrected visual acuity (BSCVA), graft clarity, pachymetry, and endothelial cell loss after 1 year were recorded. Postoperative complications and HSV recurrence were noted until the last follow-up visit., Results: All eyes were phakic with variable grades of cataract with a preoperative BSCVA of 1.0 logarithm of the minimum angle of resolution or worse. The mean follow-up period was 19.3 ± 5.4 months. After 1 year, 14 (73.7%) eyes achieved a BSCVA of 0.3 or better. Seventeen (89.5%) patients had a clear graft at the last visit without any rejection episode. One graft failed after 16 months. After 3 months, the mean pachymetry reduced from 667.1 ± 62.1 to 512.8 ± 27.1 μm (P < 0.001). The mean endothelial cell loss after 1 year was 36.7 ± 13.4%. Three (15.8%) eyes had recurrence: one with recurrent endotheliitis and 2 with dendritic keratitis despite oral ACV, which responded to oral valacyclovir and ACV eye ointment. One patient had re-recurrence of endotheliitis after 20 months., Conclusions: DMEK in persistent corneal edema after HSV endotheliitis remains challenging but has encouraging outcomes. The postoperative course may be complicated by HSV recurrence. Prophylactic oral antivirals for 1 year or more and topical antivirals are useful for the prevention of recurrence.

Background and objectives: The purpose of this study was to describe corneal sensitivity and the morphological changes of sub-basal corneal nerves using in vivo laser scanning confocal microscopy (LSCM) in herpes simplex virus (HSV) keratitis-affected eyes, and to compare with both contralateral eyes and with the eyes of patients with a previous history of herpes labialis but no history of herpetic eye disease, and with healthy patients with no history of any HSV diseases, during the acute phase of the disease and after six months. Materials and Methods: A prospective clinical study included 269 patients. All of them underwent a complete ophthalmological examination, Cochet-Bonnet aesthesiometry and LSCM within the central 5 mm of the cornea. After six months, all the patients with herpetic eye disease underwent the same examination. Serology tests of the serum to detect HSV 1/2 IgG and IgM were performed. Results: HSV-affected eyes compared with contralateral eyes, herpes labialis and healthy control group eyes demonstrated a significant decrease in corneal sensitivity, corneal nerve fibre density, corneal nerve branch density, corneal nerve fibre length and corneal nerve total branch density ( p < 0.05). During follow up after six months, corneal sensitivity and sub-basal nerve parameters had increased but did not reach the parameters of contralateral eyes ( p < 0.05). Previous herpes labialis did not influence corneal sensitivity and was not a risk factor for herpetic eye disease. Conclusions: Corneal sensitivity and sub-basal nerve changes in HSV-affected eyes revealed a significant decrease compared with contralateral eyes, and with the eyes of patients with a previous history of herpes labialis, and of healthy controls. Following six months, corneal sensitivity and sub-basal nerve parameters increased; however, they did not reach the parameters of contralateral eyes and the eyes of healthy controls. The best recovery of corneal sensitivity was seen in patients with epithelial keratitis. Herpes labialis was not a risk factor for herpetic eye disease., Competing Interests: The authors declare that they have no competing interests.

Purpose: To evaluate the long-term alterations of corneal nerves in patients with herpes simplex virus (HSV) keratitis using in vivo confocal microscopy (IVCM)., Design: Prospective, longitudinal, cross sectional., Methods: This study included 16 patients with a history of HSV keratitis and 15 age-matched normal controls. Slit-scanning IVCM was performed in all subjects at baseline and then after a mean follow-up of 37.3 ± 1.7 months in the patient group. Corneal subbasal nerve density and corneal sensation were compared between groups at baseline and follow-up., Results: At baseline, the mean subbasal nerve density was significantly lower in both affected eyes (1.4 ± 0.6 mm/mm 2 ) and contralateral unaffected eyes (6.4 ± 0.7 mm/mm 2 ) compared with the controls (14.1 ± 1.6 mm/mm 2 ; all P < .001). At the end of follow-up, the mean nerve density in affected eyes increased to 2.8 ± 0.7 mm/mm 2 (P = .006), with no significant change in contralateral unaffected eyes (6.5 ± 1.0 mm/mm 2 , P = .72). However, both eyes had lower nerve density than controls (all P < .001). Corneal sensation was significantly lower in affected eyes (2.6 ± 0.6 cm) than in the control group (6.0 ± 0.0, P < .001) and showed no significant change at the end of follow-up (2.5 ± 0.6 cm, P = .80). Corneal sensation in contralateral unaffected eyes was not different in comparison with controls at both baseline and follow up (all p > .05)., Conclusions: Our results demonstrate that although corneal nerve regeneration occurs in patients with HSV keratitis, this change is not clinically significant and does not results in changes of corneal sensation. Therefore, these patients need to be followed closely for complications of neurotrophic keratopathy and might benefit from neuro-regenerative therapies., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Objective: To describe the clinical findings of a patient with tyrosinemia type I with noncompliance to a protein-restricted diet, treated with 2-(2-nitro-4-trifluoromethylbenzoyl)-1,3-cyclohexanedione (NTBC)., Methods: Clinical findings at the initial examination and after strict compliance to a protein-restricted diet after 4 weeks follow-up are described in a patient with tyrosinemia type I on NTBC treatment, who had been treated with presumed herpetic keratitis., Results: A 10-year-old girl diagnosed with hereditary tyrosinemia type I and on NTBC treatment presented with photophobia and ocular discomfort in both eyes. An ophthalmologic examination demonstrated bilateral dendritiform epithelial lesions in the central cornea, staining faintly with fluorescein. These lesions were subsequently intermittently treated with topical antivirals for presumed herpes simplex virus keratitis and lubricant eye drops for 9 months without resolution; however, when strict compliance with a protein-restricted diet was instituted, nearly a complete resolution of the lesions was noted at the 4-week follow-up., Conclusions: Although type II tyrosinemia is known to have corneal involvement, the natural course of tyrosinemia type I has not been shown to have corneal involvement. Corneal involvement in type I tyrosinemia may be an indicator of dietary noncompliance and may show complete resolution with a strict compliance to protein-restricted diet only.

Purpose: Most of the inflammation in murine herpes simplex virus type 1 (HSV-1)-induced stromal keratitis (HSK) is due to exposure stress resulting from loss of corneal nerves and blink reflex. Corneal grafts often fail when placed on corneal beds with a history of HSK. We asked if corneal exposure contributes to the severe pathology of corneal grafts on HSV-1-infected corneal beds., Methods: Herpes simplex virus type 1-infected corneas were tested for blink reflex. Opacity and vascularization were monitored in allogeneic and syngeneic corneal grafts that were transplanted to corneal beds with no blink reflex or to those that retained blink reflex in at least one quadrant following infection., Results: Retention of any level of blink reflex significantly reduced inflammation in HSV-1-infected corneas. Corneal allografts placed on HSV-1-infected beds lacking corneal blink reflex developed opacity faster and more frequently than those placed on infected beds that partially or completely retained blink reflex. Corneal grafts placed on infected corneal beds with no blink reflex rapidly became opaque to a level that would be considered rejection. However, protecting these grafts from exposure by tarsorrhaphy prevented or reversed the opacity in both syngeneic and allogenic grafts., Conclusions: Exposure due to HSV-1-engendered hypoesthesia causes rapid, severe, persistent, but reversible opacification of both allogeneic and syngeneic corneal grafts. This opacity should not be interpreted as immunologic rejection. Exposure stress may contribute to the high rate of corneal graft pathology in patients with recurrent HSK.

Objective: To explore the clinical safety and efficacy of deep lamellar keratoplasty for corneal macula after viral keratitis., Methods: A total of 16 patients (16 eyes) of corneal macula after viral keratitis at our center from January 2009 to June 2011 received anti-virus eye-drops and then underwent deep lamellar keratoplasty when inflammation were dissolved or quiescent. And the corneal graft diaphaneity and corneal graft rejection reactions were observed., Results: All 16 patients were recovered with a success rate of 100%. After a follow-up of 18-24 months, all corneal grafts were transparent and best-corrected visual acuity was 0.2-0.6. There was no reoccurrence during the follow-up period. After a follow-up of several months, 2 of them had rejection reaction and were controlled after treatment. No rejection reaction occurred during the long-term follow-up., Conclusion: As a safe and efficacious procedure, deep lamellar keratoplasty can significantly raise vision acuity with few complications.

Neurotrophic keratitis is a degenerative disease of the cornea caused by reduced corneal innervation. Trauma, tumors, inflammatory lesions and surgical procedures can damage the first branch of the trigeminal nerve on its entire course from brainstem to and within the cornea. Loss or reduction of corneal innervation leads to a reduced aqueous phase of the tear film and due to reduced supply with neurotransmitters/trophic factors also to reduced epithelial healing capacity (impaired mitosis and migration). Combined existence of tear film deficiency and impaired epithelial healing capacity predispose to persistent epithelial defects, corneal ulcers and perforation. Early diagnosis and adequate treatment may prevent this catastrophic chain of events.

Purpose: This study was conducted to evaluate the effect of topical medroxyprogesterone (MPG) following KPro implantation in human subjects in whom donor tissue grafts had been contraindicated by high risk of failure., Methods: Outcomes of implantation of the Chirila KPro, now known as AlphaCor, were reviewed with respect to postoperative MPG therapy. Ten of 45 (22%) patients had received MPG for a period of 12 months, while 35/45 (78%) had not. MPG treatment was halted because the drug is not approved as an adjunctive treatment of KPro patients. The main outcome measures were the incidence and timing of corneal stromal melting and visual acuity., Results: Of those untreated with MPG, 34% developed a melt (mean follow-up 9.7 months), whereas of those who received MPG, 60% developed a melt (mean follow-up 28.4 months). However, mean time to melt onset for untreated cases was 8.8 months, whereas mean time to melt onset for treated cases was 23.2 months. There is a statistically significant association between time to melt onset, where melts occurred, and MPG therapy (chi2 = 0.001). In both groups, melts were strongly associated with a history of ocular HSV, which represented 17.1% of untreated and 20% of treated cases and is now considered a contraindication for AlphaCor. Preoperative visual acuities were in the range Perception Light (PL)-Count Fingers (CF) in all cases, whereas mean best postoperative best corrected visual acuity was 20/200 (range PL-20/30) in untreated cases and was 20/120 [range Hand Movements (HM)-20/30)] in MPG-treated cases., Conclusions: Although MPG may not influence the underlying incidence of melt-related complications, which are likely to be associated with other risk factors especially HSV, it may have a protective effect with regard to melt onset and severity. Controlled studies would assist evaluation of its use in this indication.

Purpose: To evaluate the safety and outcome of laser in situ keratomileusis in eyes with inactive herpetic keratitis., Methods: Prospective, interventional case series. In three eyes of three patients with inactive unilateral herpetic keratitis for a minimum period of 1 year, laser in situ keratomileusis was performed. Oral and topical acyclovir were prescribed perioperatively. No topical steroids were prescribed., Results: Preoperatively, all three eyes had corneal stromal scars with induced astigmatism in two eyes and central stromal scar in one eye with best-corrected visual acuity of 20/120, 20/25, and 20/50, respectively. Postoperatively, the three eyes achieved uncorrected visual acuity of 20/20, 20/20, and 20/50, respectively, with decreased corneal scar. None of the patients developed herpetic keratitis reactivation during a minimum follow-up of 6 months., Conclusion: Laser in situ keratomileusis was safe and effective in the treatment of refractive errors and corneal scars in three eyes of three patients with inactive herpetic keratitis.