Dear Editor,

I have just finished reading the interesting paper by Daniell et al and, being one of the first authors (Secchi AG et al, AJO, 1990, 110, 137- 42) to become interested in the topical use of Cyclosporine A in "allergic" conditions concerning the ocular surface, I would like to make a few comments - based above all on a 20-year experience in the treatment of vernal keratoconjunctivitis (VKC) with topical Cyclosporine A as my first line prescription in over 1,000 patients.

I am certainly not the only one to use this approach. Colleagues throughout the world use topical Cyclosporine A in the treatment of VKC and, particularly in the limbal forms. The tarsal forms usually improve in as little as ten days of treatment as far as symptoms are concerned, the mucus disappears, the giant papillae remain on the contrary more or less unchanged, as the corneal sterile ulcers do. No side effects have been noticed even after years of treatment, beside some corneal mild epitheliopathy and a frequent burning sensation upon instillation, which often disappears within a few weeks. My personal experience is that topical Cyclosporine A, on the overall, really changes the life in most cases of VKC patients.

Allergic keratoconjunctivitis (AKC) seems to be a rather different story. The effect of topical CsA is minimal, well below that of topical steroids, and in many cases good results are obtained only with systemic use of the drug.

The results presented by our Australian colleagues seems to be, in VKC cases, opposite to our observations. No statistical difference has been found between Restasis and the placebo, neither for symptoms nor for signs. The reason, in my opinion, is that a 0.05 % concentration of Cyclosporine A such as that present in Restasis is far too low for being active in VKC patients. We use with full satisfaction, as do our colleagues, a 1 to 2 % concentration in either olive or maize oil. In maintenance regimens even a 0.5% may be active. Lower concentrations, on the contrary, are not effective at all.

Restasis, as a major fact, is intended neither for VKC nor for AKC. Its off-label use in these clinical conditions is substantially ineffective, as our Australian colleagues have clearly confirmed.

I quite agree on the Authors' last sentence "not to recommend Restasis eye drops in steroid dependent allergic conjunctivits", but I strongly disagree on "tempering our enthusiasm": It is not topical CyclosporineA which has been shown not to be useful in VKC, it is Restasis! Will Allergan eventually provide a stronger topical preparation of Cyclosporine A? There are millions of patients suffering for VKC in the world, and steroids are not the answer while even last- generation antiallergic multivalent drugs are most often not effective enough!

Antonio G. Secchi MD
Professor of Ophthalmology and Director
Department of Ophthalmology
University of Padua, Italy
School of Medicine

ag.secchi@unipd.it

Reference:

AG Secchi, MS Tognon, A Leonardi Topical Use of Cyclosporine in the Treatment of Vernal Keratoconjunctivitis Am J Ophthal 1990, 110, 137-142.

Dear Editor,

We would like to commend authors for describing a modification to surgical technique for insertion of Molteno tube implant that eliminates the need for a donor patch scleral graft.1 The purpose of this modification is laudable however we do envisage few surgical difficulties with this modification. Firstly the creation of scleral tunnel using a curved 20 gauge microvitreoretinal (MVR) blade creates risk of mismatch between the curve of the globe and that of MVR blade and thus a risk of inadvertent intraocular entry and damage to ciliary body or lens.

Secondly the entry created by 20 gauge MVR blade is likely to be significantly larger than the outer diameter of the anterior chamber tube leading to aqueous leak around the tube entry into AC. This may increase the risk of shallow AC and hypotony in early post-operative period. This may have contributed to the frequent occurrence of corneal decompensation (20.6%) in this case series.

We believe that the traditional partial thickness scleral flap has some benefits over the scleral tunnel technique. There is no need for the scleral patch graft with partial thickness scleral flap. All glaucoma surgeons and most general ophthalmologists are familiar with this technique. Furthermore it allows the creation of AC entry under direct supervision using 22 gauge bent needle, ensuring the accurate placement of the tube in the AC and snug fit between the tube and entry site. Ability to visualize the entry site is important particularly for Ophthalmologists in their early years of Glaucoma surgery training.

Dr S P Deokule, MS, FRCSEd, FRANZCO

Prof ACB Molteno, FRCSEd

Refrences

1. J K Leong, P McCluskey, S Lightman, H MA Towler. Outcome of graft free Molteno Tube Insertion. Br J Ophthalmol 2006;90:501-505

2. ACB Molteno, MMB Van Rooyen, R Bartholomew. Implants for draining neovascular glaucoma. Br J Ophthalmol 1977;61:120-125.

Dear Editor,

I applaud the authors for attempting to address the issue of microbial contamination of preservative free (PF) eye drops in multiple application containers but wish to highlight a few points.

Although informed consent have been obtained from patients prior to analysing their eye drops, it is surprising that ethical committee approval was not sought before starting the study.

The authors have stated that the ‘safety period for multidose containers is arbitrary … not evidence based’. However, Oldham et al1 tested 21 different unpreserved multidose eyedrop formulations to establish their inherent efficacy in antimicrobial preservation and concluded that once opened by individual patients in a domiciliary situation, a 7 day in use storage life is confirmed for unpreserved eye drops containing alkaloids or antibiotics, if they are stored in the refrigerator after opening.

There has been no mention of any exclusion criterion in the selection of patients. Previous studies evaluating the issue of contamination of eye drops have either excluded patients with infected ocular surface disorders2,3 or have taken a conjunctival / corneal swab4 to evaluate whether the same microorganism was recovered from the conjunctiva and from the contaminated medication. Also, as rightly pointed out by Sher A Aslam et al5, it has been assumed in the study that the multidose containers were sterile at the time of dispensation. These two factors may invalidate the actual incidence of contamination of the eye drops in the study. Also, it does not throw any light as to whether all the contaminants isolated were truly exogenous or not.

Apparently elderly patients and those with reduced visual acuity or coordination are the ones who are most likely to inadvertently touch the tip of the dropper to the external suface. Also, the incidence of contamination of an eye drop which is being used hourly is more likely than one which is being used two or three times a day. Hence it would be interesting to know whether there is a correlation between age, visual acuity and frequency of administration of drops and incidence of contamination. Ultimately the onus remains on the medical practitioner to ensure that the unpreserved multidose eyedrops are only used in appropriate circumstances to ensure safe and effective therapy. Therefore, any significant finding in this regard may raise a question as to whether it is good practice to prescribe unpreserved multidose eyedrops to these vulnerable group of patients.

REFERENCES ----------

1. Oldham GB, Andrews V. Control of microbial contamination in unpreserved eyedrops. Br J Ophthalmol. 1996 Jul;80(7):588-91

2. Livingstone DJ, Hanlon GW, Dyke S. Evaluation of an extended period of use for preserved eye drops in hospital practice. Br J Ophthalmol. 1998 May;82(5):467.

3. Schein OD, Hibberd PL, Starck T, Baker AS, Kenyon KR. Microbial contamination of in-use ocular medications. Arch Ophthalmol. 1992 Jan;110(1):82-5.

4. Geyer O, Bottone EJ, Podos SM, Schumer RA, Asbell PA. Microbial contamination of medications used to treat glaucoma. Br J Ophthalmol. 1996 Mar;80(3):270.

5. Aslam SA, Malik N. Contamination of preservative free eye drops. eLetter: BJO (19 April 2006)

Dear Editor,

We were interested to see the letter by Mitchell et al, written in response to our earlier publication [1].

Mitchell and co-workers raise several points, the first of which is the way one handles missing data. AMD can be assessed either clinically or photographically. Rather than throw away data and run the potential of bias by excluding patients who did not have a retinal photograph, we chose to include in our analysis those people for whom we did not have a retinal photograph for one reason or another but for whom we had clinical macular grading. In separate analyses the data were not materially different if the analysis was confined to only those with photograding. In the data Mitchell et al report they excluded 15% of their sample as they lacked data and there is no evidence of what bias this may have induced.

We were very pleased to see the data from the Blue Mountains Study and recognise the advantage of incidence data over cross-sectional data. However, both cross sectional and longitudinal studies are susceptible to recall bias in the ascertainment of historical dietary intake. In nutritionally non-deficient populations people do alter their diets in response to the available commercial information. However, the bias caused by public awareness of hypothesized protective associations applies equally to both cross-sectional and longitudinal observational studies, as many know about either their disease or family predisposition to AMD before participation. However, our data were collected before the recent upsurge in publicity given to the use of nutritional supplement for macular degeneration.

The most striking thing from the data presented by Mitchell et al is that they show no evidence of a protective effect of dietary or supplement intake of Lutein and Zeaxanthin. The consistent finding of these two population-based studies must seriously challenge the association reported by previous case control studies. Case control studies are always strongly influenced by the possibility of bias in selection of controls and may frequently be influenced by the bias in the selection of. The fact that the dietary intakes in the two population-based studies is so much lower than the volunteer case control studies clearly indicates "healthy volunteer bias" as we point out in our paper (Vu et al).

The lack of effect modification by linoleic acid found in the BMES data is interesting and possibly not surprising. We found a complex U- shaped interaction between dietary intake and the risk of AMD and the decision as to where cut points are taken will strongly influence the outcome (Fig 1). It would be more informative if Mitchell et al presented their data either with the same cut points that we had used, or presented their data in a continuous form.

Nevertheless, these two studies confirm the lack of evidence to support recommendations for a specific increase in dietary intake of Lutein and Zeaxanthin to protect against macular degeneration. At the same time of course no one would encourage people to deviate from a normal healthy diet including fresh fruit and vegetables. (Vu et al, Br. J. Ophthalmol, Mar 2006; 90: 389 - 390)

Luba Robman
Allison Hodge
Catherine A McCarty
Hugh R Taylor

References

1. Vu HTV, Robman L, McCarty CA, Taylor HR, and Hodge A. Does dietary lutein and zeaxanthin increase the risk of age related macular degeneration? The Melbourne Visual Impairment Project. Brit. J. Ophthalmol, 2006; 90: 389-390.