Dear Editor,

We read with interest Rhee and co-workers' paper on intra-ocular pressure (IOP) alterations following intravitreal triamcinolone acetonide (IVTA) injection.[1] They presented the largest published patient series with the 4mg dose of IVTA (570 eyes of 536 patients). Furthermore, their comprehensive analysis concerning multiple criteria of IOP elevation (>5mmHg, >10mmHg and 30% increase from the baseline) was thorough. However we would like to address some important issues and also share our similar experience (albeit of less extent).[2,3]

First of all including both eyes of the same patient may pose bias on risk factor analysis, as there is an expected correlation between them.[4] Considering the retrospective nature of this study, authors' inclusion criteria (at least one pre-injection and one post-injection IOP recording) appears not to be adequate. For example, having a single IOP measure at six months does not exclude an earlier IOP spike. Although mean follow-up of 5.67 months seems to be satisfactory, scrutinising these numbers reveals that some eyes may have had only two months of follow-up. Establishing a minimum follow-up of at least three months as an inclusion criterion would also be desirable.[2-6] This obviously does not invalidate their justified concern on later IOP elevation, highlighted in the corresponding editorial [7] and elsewhere reported.[3,4,8-10] In our series of 150 eyes of 150 patients [3], where increase in IOP ≥5mmHg, ≥10mmHg and >30% was observed in respectively 42%, 16% and 44% of eyes receiving a 4mg IVTA dose, later elevation of IOP (after three months) was disclosed in 16.7% of eyes with secondary ocular hypertension.

Another relevant aspect is the prevalence of previous glaucomatous eyes as this may predispose to IOP elevation after IVTA injection [1,11- 14]. Agreeing with the report of Rhee et al., other series have failed to show the association between previous chronic glaucoma and secondary ocular hypertension following IVTA.[4-6] It is possible that selection bias might have influenced these results. In our study, whose sample had a 13.3% prevalence of chronic glaucoma before injection, we found previous glaucoma to be predictive of secondary ocular hypertension after IVTA (p=0.004), with a relative risk (RR) of 2.17 (1.38<95%CI[confidence interval]<3.41). In fact, mean baseline IOP was 16.7±4.4mmHg in glaucomatous vs. 14.6±3.0mmHg in nonglaucomatous eyes and increased to a mean peak of 23.8±7.5mmHg and 18.9±5.4mmHg, respectively. We thus believe that pre-existent glaucoma of variable severity may be a confounding factor and contribute to the wide range in prevalence and severity of IOP elevation in various series [3], in addition to definitions of IOP rise, sample size and range of follow- up.[1]

Finally, baseline IOP has gained recent concern as a possible risk factor for subsequent secondary ocular hypertension following IVTA.[1,4] We also found that baseline IOP≥16mmHg was a significant risk predictor (RR=2.31; 1.32<95%CI<4.05; P=0.003). Nevertheless it is not known whether reduction of baseline IOP with hypotensive drops prior to IVTA injection would modify this risk.[3] It is possible that this could occur in eyes with pre-existent glaucoma under topical treatment.

We congratulate Rhee and co-workers on their comprehensive report and hope future prospective studies further mitigate some of these questions.

Daniel V. Vasconcelos-Santos, MD
Érika P. Magalhães, MD, PhD
Márcio B. Nehemy, MD, PhD

Federal University of Minas Gerais, Belo Horizonte, Brazil.

References

1. Rhee DJ, Peck RE, Belmont J, Martidis A, Liu M, Chang J, Fontanarosa J, Moster MR. Intraocular pressure alterations following intravitreal triamcinolone acetonide. Br J Ophthalmol. 2006;90:999-1003.

2. Vasconcelos-Santos DV, Costa LT, Magalhães EP, Accioly SL, Nehemy PG, Nehemy MB. Efeito da triancinolona intravítrea na pressão intra- ocular. Rev Bras Oftalmol, 2005; 64:32-36.

3. Vasconcelos-Santos DV, Magalhães EP, Nehemy MB. Secondary ocular hypertension following intravitreal triamcinolone injection in Brazil: incidence and risk factors. Clin Exp Ophthalmol, submitted.

4. Smithen LM, Ober MD, Maranan L, Spaide RF. Intravitreal triamcinolone acetonide and intraocular pressure. Am J Ophthalmol. 2004;138:740-3.

5. Jonas JB, Degenring RF, Kreissig I, Akkoyun I, Kamppeter BA. Intraocular pressure elevation after intravitreal triamcinolone acetonide injection. Ophthalmology 2005;112:593-8.

6. Jonas JB, Kreissig I, Degenring R. Intra-ocular pressure after intravitreal injection of triamcinolone acetonide. Br J Ophthalmol. 2003;87:24-27.

7. Conway MD. The problem of pressure elevation associated with intravitreal triamcinolone. Br J Ophthalmol. 2006;90:934-5.

8. Jonas JB. Intraocular availability of triamcinolone acetonide after intravitreal injection. Am J Ophthalmol 2004;137:560-2.

9. Jonas JB, Degenring RF, Kamppeter BA, Kreissig I, Akkoyun I. Duration of the effect of intravitreal triamcinolone acetonide as treatment for diffuse diabetic macular edema. Am J Ophthalmol. 2004;138:158-60.

10. Meyer CH, Mennel S, Schmidt JC. Intravitreal triamcinolone acetonide may increase the intraocular pressure even in vitrectomized eyes after more than 3 months. Am J Ophthalmol. 2005;140:766-7.

11. Armaly MF. Statistical attributes of the steroid hypertensive response in the clinically normal eye. I. The demonstration of three levels of response. Invest Ophthalmol 1965;4:187-97.

12. Becker B. Intraocular pressure response to topical corticosteroids. Invest Ophthalmol 1965;26:198-205.

13. Jones R 3rd, Rhee DJ. Corticosteroid-induced ocular hypertension and glaucoma: a brief review and update of the literature. Curr Opin Ophthalmol. 2006;17:163-7.

14. Park HY, Yi K, Kim HK. Intraocular pressure elevation after intravitreal triamcinolone acetonide injection. Korean J Ophthalmol. 2005;19:122-7.