Editor,
We read with interest the article by Ishioka and coworkers, in which the authors studied the effect of trabeculectomy with and without mitomycin C in post-keratoplasty glaucoma. The authors conclude that trabeculectomy with mitomycin C showed better results for glaucoma following penetrating keratoplasty. We congratulate the authors for an excellent study. We have published similar observations on trabeculectomy with mitomycin C for post- keratoplasty in 1997.[1] The salient features of this study are worth mentioning as literature on mitomycin C augmented trabeculectomy in post-keratoplasty glaucoma is limited.

In the study by Sharma and coworkers trabeculectomy with mitomycin C (0.2 mg/ml for 2.5 minutes) was performed in 16 eyes of 16 patients for medically uncontrolled glaucoma following penetrating keratoplasty. The mean pre-trabeculectomy IOP with maximal medical therapy was 34.6 mm Hg (range 24 to 45 mm Hg). The mean IOP following trabeculectomy with mitomycin C was 14.2 mm Hg (range 8 to 36 mm Hg) by the end of follow-up of 14.2 months (range 8 to 32 months). Fourteen eyes (87.5%) had complete success, one eye (6.25%) had qualified success and one eye (6.25%) had failure. All the patients had either better than or maintained pre-operative visual acuity. None of the patients developed postoperative complications such as shallow anterior chamber, epithelial defect of hypotony. Earlier Khatana et al[2] presented in ARVO showed reduction of IOP following trabeculectomy with mitomycin C in most of their patients. In addition to the efficacy, safety of trabeculectomy with mitomycin C for post-keratoplasty glaucoma reported is a major concern. Mitomycin C as an adjunct to trabeculectomy has been safe for corneal endothelium.[3] In an experimental study on rabbit eyes, the peak aqueous level of mitomycin C after topical application (0.4 mg/ml) was 0.03 ± 0.02 mg/ml.[4] This aqueous concentration was considered above the therapeutic level for inhibition of subconjunctival fibroblast proliferation but below the level known to cause endothelial toxicity.[4] In studies by Sharma et al[1] and Khatana et al,[2] mitomycin augmented trabeculectomy caused no damage to the clear penetrating grafts.

Our observations were in accordance with those by Ishioka, et al that in medically uncontrolled glaucoma following penetrating keratoplasty, trabeculectomy with mitomycin C may be considered unless there is a contraindication to the use of adjuvant. However, the authors may have inadvertently missed our earlier report.

References
1. Sharma A, Kumar S, Ram J, et al. Trabeculectomy with mitomycin C for post-keratoplasty glaucoma: A preliminary study. Ophthal Surg Lasers 1997;28:891-5.
2. Khatana AK, Olivier M, Shin DH, et al. Safety and efficacy of adjunctive mitomycin-C in filtration surgery in eyes with corneal grafts. Invest Ophthalmol Vis Sci 1993;34(Suppl):1099.
3. Anglade E and Dreyer E. The effect of mitomycin-C and 5-fluorouracil on corneal endothelium in trabeculectomy surgery. Invest Ophthalmol Vis Sci 1993;34(Suppl):730A.
4. Eezuduemboi RD, Sarraf D, Wilson MR, et al. Aqueous and vitreous concentration of mitomycin following topical administration. Invest Ophthalmol Vis Sci 1993;34(Suppl):726.

Editor,
The work of West and Gregor again points out the importance of sclerotomy complications following pars plana vitrectomy. They demonstrate that, even in the hands of a skillful and experienced surgeon, vitreous hemorrhage after vitrectomy for diabetic retinopathy is common and requires vitreous cavity washout (VCWO) in 12% of cases. In their series, over half of the eyes had detectable fibrovascular ingrowth (FVI) as the cause of the hemorrhage. Interestingly, in this case series of 159 eyes, no occurrences of anterior hyaloidal fibrovascular proliferation (AHPV) were noted.

Definition of the relationship between these two entities has been controversial, to say the least. Part of the controversy is due to a misunderstanding of the nature and pathogenesis of FVI. As McLeod points out in his editorial, FVI is a term that has been used inadvisedly, suggesting the episcleral tissue grows into the eye through the sclerotomy incision [1]. While episcleral tissue, scleral fibroblasts, and ciliary epithelium all contribute, the majority of the fibroproliferative healing of a sclerotomy originates from the uvea of the ciliary body [2]. In normal wound healing, early fibrovascular proliferation in the incision is followed by its involution and contraction, with the result being the small scar seen at the internal aspect of a healed sclerotomy [2].

Inevitably, because of the proximity of the vitreous base and anterior hyaloid, vitreous strands are adherent to the wound and fibrous tissue extends a short way into the vitreous body. This tissue may contain blood vessels, even with normal healing. From this perspective, all sclerotomy wounds heal with fibrovascular ingrowth. That is, ingrowth of tissue from the eye wall extends into the vitreous cavity. Fortunately, only in unusual circumstances does this process become exaggerated and result in what clinicians have termed FVI with its concomitant intraocular mischief [3].

McLeod pointed out that ischemia is an important factor in inducing FVI and that it is seen mainly following vitrectomy for ischemic retinopathies. I agree that this is the case if one includes anterior proliferative vitreoretinopathy (APVR) in this group. Patients with APVR who have had previous vitrectomy frequently have an excessive amount of fibrovascular scarring from their sclerotomies that significantly affects the pathologic anatomy of the basal vitreous and its environs. These patients, however, often have had extensive scleral buckling and cryopexy, processes which undoubtedly induce some anterior ischemia in themselves [2]. In the series of West and Gregor, no patient was found to have a retinal detachment utlrasonographically or at the time of VCWO. In the original description of AHFP, most of the patients had retinal detachments that had required scleral buckling [4]. Since retinal detachment and scleral buckling exacerbate anterior ischemia, it is likely that AHFP, which is fibrovascular proliferation into the vitreous base from the retina and ciliary body, is induced by an ischemic drive similar to that casing FVI. The two entities exist on a continuum. When there is a surgical injury such as a sclerotomy, with disruption of tissue and inoculation of blood into the surrounding vitreous, excessive proliferation may occur with less induction than that which causes AHFP. Personally, although I have observed cases of AHFP without having previous vitrectomy, I have never seen a case of post-vitrectomy AHFP without some concurrent FVI.

Finally, I'd like to make two other points. The first is that West and Gregor used clinical criteria to determine whether or not FVI existed and caused the recurrent vitreous hemorrhage. I have observed vitreous hemorrhage in an autopsy eye from what grossly appeared to be a normally healed sclerotomy wound [5]. Microscopically, that white scar contained numerous capillaries that were the source of the hemorrhage. Therefore, it may be that some of their non-FVI patients might actually have had vitreous hemorrhage from a sub-clinical FVI. Furthermore, FVI can involute with time, becoming less vascular in its appearance. So, the frequency of FVI may be even higher than reported. Lastly, I agree that episcleral sentinel vessels, externally entering the wound site, sometimes, but now always, indicate a possible FVI. These vessels are the result of a high degree of metabolic activity during the healing of sclerotomy wounds and may persist even though wound fibroplasia becomes involutional and clinically unimportant. Similar vessels are seen microscopically in the ciliary body [2]. When present, sentinel[2] vessels should raise our suspicions of FVI; but they do not rule it in, nor does their absence rule it out.

References
1. McLeod D. Entry site neovascularisation after diabetic vitrectomy. Br J Ophthalmol 2000;84:810-811.
2. Kreiger A. The pars plana incision: experimental studies, pathologic observations, and clinical experience. Trans Amer Ophthalmol Soc 1991;89:549-621.
3. Kreiger A, Straatsma B, Foos R. Incisional complications in pars plana vitrectomy. Mod Prob Ophthalmol 1977;18:210-233.
4. Lewis H, Abrams G, Williams G. Anterior hyaloidal fibrovascular proliferation after diabetic vitrectomy. Am J Ophthalmol 1987;104:607-613.
5. Foos R, Kreiger A, Nofsinger K. Pathologic study following vitrectomy for proliferative diabetic retinopathy. Retina 1985;5:101-106.

Editor,
I was interested to read the case report of branch retinal artery occlusion (BRAO) in a 69 year old male that was presumed to have been caused by sildenafil.

In addition to transient cardiac arrhythmia, the authors speculate that the underlying mechanism of arterial occlusion may have been a sudden rise in intra-ocular pressure caused by Viagra. They do not mention whether the arterial occlusion had any relationship to coitus. If the speculation that Viagra did elevate IOP is correct, the physical activity of coitus would tend to reduce intraocular pressure (1) possibly normalising the IOP. On the other hand, sexual arousal has been found to precipitate angle closure glaucoma in anatomically predisposed eyes (2, 3) in which case the elevated IOP, if indeed it was ever present, possibly may not have been caused by Viagra.

The absence of risk factors in the reported patient should not automatically implicate Viagra as the cause of BRAO, since the underlying aetiology is unclear in a sizeable minority of patients with retinal arterial occlusive disease (4). Coitus has previously been associated with amarosis fugax (5), and Tripathi and O'Donnell acknowledge that many patients using Viagra would be at a high risk of vascular occlusions anyway.

The authors recommend that branch retinal artery occlusion "should be…discussed with all patients started on sildenafil". It would place an unacceptable burden on both doctors and their patients if they had to discuss every side effect of prescribed drugs, especially if the possible side effect has only ever been reported once in many tens of millions prescriptions. In many instances, even if the time was available for such discussion, this would probably generate unnecessary anxiety and cause further harm to the patient by reducing patient compliance.

I would avoid alarming patients with speculation that Viagra may cause blindness until more compelling evidence is available to justify this warning.

1) Harris A, Arend O, Bohnke K, et al. Retinal blood flow during dynamic exercise. Graefes Arch Clin Exp Ophthalmol. 1996;234:440-4.
2) Friedberg DN, Fox LE. Blurred vision during sexual arousal associated with narrow-angle glaucoma. Am J Ophthalmol 1999;128:647-648.
3) Markovits A. Ophthalmodynia hypertonica copulationis: a new syndrome? Can J Ophthalmol 1974:9:484-485.
4) Haase CG, Buchner T. Microemboli are not a prerequisite in retinal artery occlusive diseases. Eye 1998;12:659-662.
5) Teman A, Winterkorn J, Weiner D. Transient monocular blindness associated with sexual intercourse. N Engl J Med 1995;333:393

Editor,
I am a 76-year-old suffering from myopic degeneration (is this ARMD?).I have been operated for cataract on my left eye with no significant improvement. I am strongly convinced that the usual measurement of visual acuity is almost meaningless. The major problem I find in practical life is the lack of adequate sensitivity to contrast. For example, in my bank they print their copy report with a gray ink (for reasons of elegance, I suppose). These are not readable to me, but if I use a scanner copy they become immediately readable. In the seventy years that I have undergone eye tests I do not remember one single time that somebody would care about contrast sensitivity. Is there at least a standard procedure to measure contrast sensitivity about which I could inquire and possibly use to check my progress?
Thank you.