1. PHOTODYNAMIC THERAPY FOR CORNEAL NEOVASCULARIZATION IN HERPES SIMPLEX KERATITIS
Aurthors have no financial interest.
N. Pastora-Salvador, A. Boto-Bueis, J. Peralta-Calvo, S. Llorente-González, I. Canal-Fontcuberta, B. SanJosé-Valiente
Hospital La Paz, Madrid (Spain)

2. INTRODUCTION
Long-term corneal neovascularization (CoNV) can produce permanent anatomic corneal changes, worsening vision and causing chronic discomfort for patients.
Herpes simplex keratitis (HSK) is a frequent cause of secondary CoNV.
After an early phase in which the neovessels development is highly VEGF-dependent, a pericytal coating and a progressive increase in the number of layers of basal membrane may determine VEGF-independency (1).
So, theoretically, inhibition of active long term neovessels probably require physical or mechanical therapies.
(1) C Cursiefen, C Hofmann-Rummelt, M Küchle, and U Schlötzer-Schrehardt. Pericyte recruitment in human corneal angiogenesis: an ultrastructural study with clinicopathological correlation. Br J Ophthalmol. 2003;87(1):101-6.

3. MATERIAL & METHODS EXCLUSION CRITERIA INCLUSSION CRITERIA
Prospective interventional, non controlled case serie study.
Consecutive recruitment of patients on follow-up for HSK from January to December 2008.
Informed consent (patients were informed about the experimental nature of the procedure and known adverse effects, obtaining a written consent).
INCLUSSION CRITERIA
EXCLUSION CRITERIA
acute ocular herpes in the previous 12 weeks
any other previous or concomitant corneal or ocular disease, or surgery distinct than cataract
phacoemulsification in the previous 6 months
non controlled systemic disease
nefropathy, hepatitis or significant hepatopathy, porphyria or porphyrins sensitivity
pregnancy
age >18 years
active CoNV secondary to HSK for the ≥3 previous months
2) progressive lipid exudation
3) conventional medical treatment failure (topical corticosteroids 4 times daily for 1 month).

4. MATERIAL & METHODS: PROCEDURE
PHOTOSENSITIZER AND PHOTOACTIVATOR
VERTEPORFIN (6mg/mm2 of body surface) in lipid formulation diluted with 5% of dextrose till a volume of 30ml.
10 minutes antecubital vein intravenous infusion.
Laser application started 15 minutes after the infusion began (infrared light laser of 689nm mounted on a slitlamp).
Power intensity of 600mW/cm and total light dose of 50 J/cm2.
Guiding spot focused on stromal neovessels, with local applications of 83 seconds.
PRETHERAPY
ORAL ANTIHERPETIC PROFILAXIS at least from 48 hours prior to 2 weeks later.
TOPICAL CORTICOSTEROIDS/6-8 hours, at least from 48hours prior.
THERAPY APPLICATION
The entire area with visible neovessels was treated.
With large neovascular areas, we employed several spots, with mild superposition (less than 25%). Application was iniciated peripherally, from limbal to central corneal area.
Visual axis was not treated.
POSTHERAPY TREATMENT
CIPROFLOXACIN EYEDROPS/8 hours 1week
TOPICAL CORTICOSTEROIDS/6 hours, slowly tapered.
light ocular and skin protection for 3 and 7 days, respectively. 2 1 3

5. MATERIAL & METHODS: EVALUATION OUTCOME MEASURES
ICONOGRAPHIC (2 blind evaluators). ImageJ.
QUANTITATIVE
PERCENTAGE (%) OF CORNEAL AREA WITH NEOVESSELS
% OF CORNEAL AREA WITH PATHOLOGY
NUMBER OF LIMBAR CORNEAL NEOVESSELS
SEMIQUANTITATIVE
CORNEAL OPACITY (from 0 to 3)
Global subjective corneal state (comparing before and after PDT: worse-equal-better)
2. CLINICAL
1. HERPETIC OUTBREAKS/YEAR
1. TOTAL
2. IMMUNOLOGIC (insterstitial immune keratitis, non-linear endotheliitis)
3. INFECTIOUS (epithelial dendrite, geographic ulcer, marginal keratitis, necrotizing insterstitial keratitis or linear endotheliitis)
2. Intraocular Pressure (IOP)
3. Subjetive perception by patients
4. Visual Acuity (VA)
Images: example of iconographic cuantitative examination

6. RESULTS I Nº patients: 9 (8 females) DEMOGRAPHICS (mean±SD) [range]:
Age: 54,6±12,4 years [34-69y]
Pretherapy follow-up: 39,2±34,6 months [13-120m]
PDT sesions: 1,2±0,4 [1-2]
Postherapy follow-up: 29,6±11,8 months [10-43m]
Table 1-click

7. RESULTS: ICONOGRAPHIC DATA
10 months after PDT
VA: 20/40
Case 9
VA: 20/80
p<0,05
Global corneal state Pos-PDT: 9/9 better
VA: 20/40; 41 months pos-PDT
VA: 20/80
p<0,05
p<0,05

8. RESULTS: CLINICAL DATA
75,2%
PRE-PDT
p<0,05
76,7%
VISUAL ACUITY
IOP
p<0,05
p>0,05
mmHg
PRE-PDT
POS-PDT

9. REPORT OF CASES 60 years-old female.
Revascularization occurred 2 months after PDT. Retreatment with a 2º sesion of PDT led to vascular occlusion.
Case 4
VA: 20/30
35 months after PDT
VA: 20/20
Revascularization
Case 5
36 years-old female.
Active CoNV despite medical treatment resolved with PDT.
36 months after PDT
VA: 20/120
VA: 20/160

10. ADVERSE EFFECTS RECANALIZATION REVASCULARIZATION
Mild-moderate transient postoperative photofobia (3 cases)
Intrastromal hematic extravasation (8 cases)
Mild stromal thinning (2 cases)
RECANALIZATION
Reopening of treated vessels.
REVASCULARIZATION
Vascularization of treated zone with different neovessels than those primarily treated.

11. DISCUSSION
Our study showed that PDT with Verteporfin was effective and safe for corneal neovascularization in HSK, because:
can effectively occlude long term corneal neovessels (however, several sessions may be necessary).
can reduce corneal area with neovascularization and disease, number of corneal neovessels, and corneal opacity.
can help to reduce herpetic outbreaks/year.
6/9 patients perceived PDT effects as beneficial.

12. DISCUSSION
We can not confirm if PDT has any direct effect on herpes hosted by the cornea, but PDT antiherpetic effects has been proposed elsewhere as in herpes labialis.
In our study, vascular stromal occlusion was associated with reduction in herpetic outbreaks. We believe it may be related to interruption of the corneal afferent-efferent immune arc, impending inflammatory cells to mount insterstitial reactions.
We recomend to consider PDT for corneal neovascularization resistant to medical treatment in patients with recurrent interstitial immune HSK.
(2) Sperandio FF, Marotti J, Aranha AC, Eduardo Cde P. Gen Dent. 2009;57(4): Photodynamic therapy for the treatment of recurrent herpes labialis: Preliminary results.