Dear Editor

We thank Dr Wong and colleagues very much for their interest in our study,[1] we agree with them that comparing a single preoperative measurement with the best out of a series of postoperative measurements gives a tendency towards a falsely high increase in visual acuity after the triamcinolone acetonide injection. That there was an increase in visual acuity after the injection in some patients, however, may have been demonstrated in Table 1 giving the visual acuity measurements prior to, and after, the application of triamcinolone acetonide. At 1 and 2 months, the difference to the preoperative values was significant with a p-values of 0.04. Unfortunately, the values are described as non significant what is a typographical error in the manuscript. I regret this fault. The authors agree with Dr Wong and colleagues, that the effect of triamcinolone acetonide is temporary, and that repeated injections may be necessary. In some patients, repeated intravitreal injections of triamcinolone acetonide were associated with repeated re-increase in visual acuity.[2]

We also agree with Dr Wong and coworkers, that comparing the preoperative intraocular pressure measurement with the highest value during the follow-up again falsely increased the number of ocular hypertensive subjects after the injection. In this matter, however, it was not in favour of the treatment modality since it artificially increased the number of patients with unwanted side-effects. Concerning the number of patients with very high intraocular pressure values after the injection, a preliminary analysis shows that about 1% of the eyes injected will need filtering surgery (own data).

The authors would like to thank Dr Wong and colleagues for constructively commenting on the study and pointing out, as did the authors, that the intravitreal injection of triamcinolone acetonide as treatment of exudative macular degeneration is still in clinical evaluation and that its therapeutic effect has not been proved so far. This may be even more important, as a recent randomised study using 4 mg of triamcinolone acetonide did not demonstrate an effect on the risk of loss of visual acuity during the first year of the study in eyes with classic choroidal neovascularization.[3] A significant antiangiogenic effect, however, was found 3 months after treatment. In view of the anti- angiogenic, anti-inflammatory and anti-oedematous effect of intravitreal triamcinolone, it may show that further randomised trials using different dosages of triamcinolone acetonide in eyes with different types of subfoveal neovascularization may be warranted.

References

(1) Jonas JB, Kreissig I, Degenring R. Intraocular pressure after intravitreal injection of triamcinolone acetonide. Br J Ophthalmol 2003;87:24-7.

(2) Jonas JB, Kreissig I, Degenring RF. Repeated intravitreal injections of triamcinolone acetonide as treatment of progressive exudative age-related macular degeneration. Graef Arch Clin Exp Ophthalmol 2002;240:873-4.

(3) Gillies MC, Simpson JM, Luo W, et al. A randomised clinical trial of a single dose of intravitreal triamcinolone acetonide for neovascular age-related macular degeneration: one-year results. Arch Ophthalmol 2003;121:667-73.

Dear Editor

We read the article on intravitreal triamcinolone injections for exudative age-related macular degeneration with interest.[1] The paper stated that visual acuity increased significantly (p <_0.001 from="from" _0.16="_0.16" _0.11="_0.11" to="to" a="a" mean="mean" maximum="maximum" of="of" _0.23="_0.23" _0.17.="_0.17." the="the" authors="authors" therefore="therefore" picked="picked" best="best" one="one" up="up" _10="_10" postoperative="postoperative" visual="visual" acuity="acuity" measurements="measurements" and="and" compared="compared" it="it" with="with" single="single" preoperative="preoperative" measurement.="measurement." this="this" is="is" misleading="misleading" reader="reader" regarding="regarding" true="true" effectiveness="effectiveness" treatment.="treatment." p="p"> The Macular Photocoagulation Study Group found that the differences in between two repeated tests was one line or more in 13% of cases and the differences were greatest in patients with visual acuity of 20/100 or worse.[2] By taking up to 10 postoperative measurements, Jonas et al. greatly increased the chances of a positive result. The difference between mean pre-injection 0.16 (20/125 or 6/36) and best mean postoperative 0.23 (20/87 or 6/26) was less than one line on the Snellen chart.

Table 1 gave the mean visual acuity pre-injection and at various time intervals post-injection. At 1 and 2 months, the p values were 0.04. It was unclear whether the p values were one or two tailed but both were described as not significant (NS) in table 1. Multiple significance testing at each of a number of time points is generally not recommended - if it is done, some kind of adjustment to the p values is needed.[3,4] Looking at the results presented table 1, the readers might conclude that triamcinolone had a transient and doubtful beneficial effect on the visual acuity.

The authors go on to further analyse the results into improvements of 3 and 6 or more lines. The vision was tested on a Snellen chart which has irregular steps. Three or 6 lines do not therefore represent a constant change in visual angle (as in a logMAR chart) and therefore the analysis was confusing.

Variations in intraocular pressure of 5 or 6 mmHg occur diurnally in normal individuals as well as glaucomatous patients.[5-7] Whilst there is little doubt that triamcinolone may affect the intraocular pressure, the comparison of the baseline with the highest (p <_0.001 was="was" misleading="misleading" as="as" the="the" comparison="comparison" of="of" highest="highest" with="with" that="that" at="at" _7="_7" months="months" p0.001.="p0.001." more="more" interest="interest" might="might" be="be" number="number" patients="patients" who="who" had="had" very="very" high="high" levels="levels" range="range" extended="extended" to="to" _64="_64" mmhg="mmhg" and="and" whether="whether" these="these" intraocular="intraocular" pressures="pressures" responded="responded" treatment.="treatment." p="p"> The authors’ experience in using triamcinolone is well recognised. We congratulate them on an otherwise excellent piece of work.

References

(1) Jonas JB, Kreissig I, Degenring R. Intraocular pressure after intravitreal injection of triamcinolone acetonide. Br J Ophthalmol 2003;87(1):24-7.

(2) Blackhurst DW, Maguire MG. Reproducibility of refraction and visual acuity measurement under a standard protocol. The Macular Photocoagulation Study Group. Retina 1989;9(3):163-9.

(3) Altman DG. Practical Statistics for Medical Research. London: Chapman and Hall, 1991.

(4) Matthews R. The numbers don't add up. New Scientist 2003;177(2385):28.

(5) Pointer JS. The diurnal variation of intraocular pressure in non- glaucomatous subjects: relevance in a clinical context. Ophthalmic Physiol Opt 1997;17(6):456-65.

(6) De_Vivero C, O_Brien C, Lanigan L, Hitchings R. Diurnal intraocular pressure variation in low-tension glaucoma. Eye 1994;8(Pt5):521-3.

(7) Smith J. Diurnal intraocular pressure. Correlation to automated perimetry. Ophthalmology 1985;92(7):858-61.