Evaluating Adjunctive Cryopreserved Amniotic Membrane Treatment in Herpes Simplex Dendritic Keratitis

Study Overview
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Brief Summary
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To prospectively evaluate the effectiveness of Prokera Slim in adults with primary or recurrent herpetic epithelial keratitis in terms of visual function, corneal opacity, time to resolution, cost of care, number of patient visits.

Detailed Description
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Cryopreserved amniotic membrane (AM) contains anti-inflammatory, anti-scarring and antiangiogenic effects known in treating many ocular surface diseases. This notion is further strengthened by many studies showing that amniotic membrane can effectively control inflammation in HSV stromal keratitis in a murine model of HSV necrotizing keratitis and surgical application in  7 human studies of epithelial and stromal HSV keratitis with or without an adjuvant antiviral therapy. More importantly, PROKERA SLIM in conjunction with oral acyclovir has been shown to facilitate the ease of early intervention to accelerate restoration in herpetic keratitis in 2 case series of 5 eyes. However, a formal prospective study has not been performed.

Official Title
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A Pilot Study Evaluating Adjunctive Cryopreserved Amniotic Membrane Treatment for Primary or Recurrent Herpes Simplex Dendritic Keratitis

Conditions
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Herpes Simplex Dendritic Keratitis

Intervention / Treatment
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* Device: Prokera Slim
* Other: Standard of Care


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: The subject (male or female) is at least 18 years of age. The subject is presenting with primary or recurrent herpetic dendritic epithelial keratitis based on investigator judgement The subject is presenting with acute (within 30 days) herpetic dendritic epithelial keratitis The subject is willing to comply with all study procedures and is able to consent. Exclusion Criteria: Clinical signs of a cause other than herpes simplex virus Presence of corneal ulcer with or without microbial infection Lid surface abnormalities or conjunctival scarring that affect lid function in either eye Atopic disease History of penetrating keratoplasty Active stromal keratitis or iritis Presence of systemic or ocular infection or inflammation that is not related to herpes simplex virus (such as Sarcoidosis, Cogan syndrome, atopy, Lyme disease, Syphilis, mumps, Epstein-Barr virus) Ocular surface malignancy History of recent ocular surgery/trauma, which could affect corneal sensitivity, e.g., corneal transplantation, LASIK A medical or ocular condition, or a personal situation, which in the principal investigator's opinion, is not appropriate for participation in the trial Current enrollment in another interventional drug or device study or participation in such a study within 30 days of anticipated entry into this study Not capable of providing informed consent

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 100 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Control Arm<br>All subjects enrolled in the study will receive the standard of care that includes epithelial debridement of all dendrites via Weck-Cel Cellulose sponge, topical prophylactic antibiotics (e.g., Ocuflox QID (four times daily) for one week) and oral acyclovir (400 mg 5x/day for 10 days for primary cases but tapered to 2x/day for 3 months for recurrent cases based on investigator's discretion). | Other: Standard of Care<br>* Standard of care includes epithelial debridement of all dendrites via Weck-Cel Cellulose sponge, topical prophylactic antibiotics (e.g., Ocuflox QID for one week) and oral acyclovir (400 mg 5x/day for 10 days for primary cases but tapered to 2x/day for 3 months for recurrent cases based on investigator's discretion).<br>|
| Active Comparator: Treatment Arm<br>All subjects enrolled in the study will receive the standard of care that includes epithelial debridement of all dendrites via Weck-Cel Cellulose sponge, topical prophylactic antibiotics (e.g., Ocuflox QID for one week) and oral acyclovir (400 mg 5x/day for 10 days for primary cases but tapered to 2x/day for 3 months for recurrent cases based on investigator's discretion). The treatment arm will also receive the placement of PROKERA SLIM for 5-7 days. A second PROKERA SLIM may be applied based on investigator's discretion. For patients with bilateral involvement only the worse eye will be enrolled for the treatment arm. | Device: Prokera Slim<br>* Placement of an Adjunctive Cryopreserved Amniotic Membrane Treatment.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time-dependent change in BCVA by 1 weeks | The BSCVA was recorded at 4 meters by a refractionist certified for the study using a protocol adapted from the Age-Related Eye Disease Study using Early Treatment Diabetic Retinopathy Study charts: chart R(2110), chart 1(2111), and chart 2(2112) (Precision Vision, Woodstock, IL). | 1 week | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of patients with complete epithelialization by 1 week | Proportion of patients with complete epithelialization by 1 week, graded 0, SPK 1+, SPK 2+, SPK 3+ (SPK is Superficial Punctate Keratitis) | 1 week | 
| Time-dependent change in BCVA by 2 weeks | The BSCVA was recorded at 4 meters by a refractionist certified for the study using a protocol adapted from the Age-Related Eye Disease Study using Early Treatment Diabetic Retinopathy Study charts: chart R(2110), chart 1(2111), and chart 2(2112) (Precision Vision, Woodstock, IL). | 2 weeks | 
| Time-dependent change in BCVA by 2 months | The BSCVA was recorded at 4 meters by a refractionist certified for the study using a protocol adapted from the Age-Related Eye Disease Study using Early Treatment Diabetic Retinopathy Study charts: chart R(2110), chart 1(2111), and chart 2(2112) (Precision Vision, Woodstock, IL). | 2 months | 
| Proportion of patients with corneal opacity at 2 months | Proportion of patients with corneal opacity at 2 months, graded 0, 1+, 2+, 3+, and 4+. | 2 months | 
| Proportion of patients with recurrence by 2 months | Proportion of patients with recurrence by 2 months counted individually | 2 months | 
| Change in corneal sensitivity from baseline to 2 months | Change in corneal sensitivity from baseline to 2 months using Cochet-Bonnet esthesiometer, graded 0/4, 1/4, 2/4, 3/4, and 4/4. | 2 months | 
| Change in conjunctival inflammation at 1 week | Conjunctival inflammation graded by investigator as none (0), mild (1), moderate (2), and severe (3) | 1 week | 
| Change in conjunctival inflammation at 2 week | Conjunctival inflammation graded by investigator as none (0), mild (1), moderate (2), and severe (3) | 2 week | 
| Total number of extra patient visits, treatments, and procedures throughout study | Total number of extra patient visits, treatments, and procedures throughout study, counted individually by type | 2-3 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Prokera, Adjunctive Cryopreserved Amniotic Membrane, Prokera Slim