BASIC INVESTIGA TION S hort-Term Eff e c to f Top i c a l Dorzo l am i de Hydro c h l or i de on I ntra s troma l Cornea l Pre ss ure i n Rabb i t Cornea s I nV i vo Miguel A. T eus, MD, PhD,*†‡ Gema Bolı ´ var , MD,* Jorge L. Alio ´ , MD, PhD,§¶ and Isaac Lipshitz, MD k Purpose: T o evaluate theeffect of topical dorzolamide on the intrastromal corneal pressure (ICP) in rabbit corneas invivo. Methods: This is an interventional prospective study. T opical dorzolamide was applied to7 eyes of 7 male New Zealand rabbits 3 times daily for 3 consecutive days. The ICP changes were recorded with a pressure transducer connected to the midperipheral cornea. The ICP wasmeasured in the same manner in7 eyes of 7 male New Zealand rabbits that were treated with artificialtears (control group). Results: The ICP values averaged 2 6.2 6 3.2, 2 10 6 5.8, and 2 12.5 6 8.7 mm Hg at 15, 30, and 45 minutes in thecontrol group, respectively. In the dorzolamide-treated eyes, the ICP readings were 1.8 6 3.4, 2 0.28 6 4.3, and 2 1.8 6 5.3 mm Hg atthe same time points, respectively. The differences in the ICP between both groups were significantlydifferent at all time points (P = 0.004, P = 0.005, and P = 0.02). Conclusions: Measuring ICP is a valid and sensitive method to evaluate invivo theendothelial function. Thismethod seems tobe more sensitive than measuring the central cornealthickness or the corneal deswelling rate in detecting changes in the corneal physiology with the use of topical dorzolamide. Key Words: intrastromal corneal pressure, dorzolamide, endothelial function (Cornea 2009;28:206–210) C ornealtransparency is critical for visual function, and this is clearly a unique propertyof this tissue. A functionally intact endothelium is necessary to maintain stromal clarity because it regulates corneal hydration. 1 Thecornea is thought to maintain its deturgescence by a pump–leak mechanism in which theendothelial cells act both as a barrier to fluid movement from theanterior chamber into the stromaand as an active pump to move fluid out of the stroma into theaqueous humor . 1–3 If the activityof theendothelial pumpdecreases, then the stromal water contentincreases, leading to increased cornealthickness, followed by loss of cornealtransparency (corneal edema). 1–4 There has been somecontroversy aboutthe possibility that topical carbonic anhydrase inhibitors might induce irreversible corneal endothelial decompensation in com- promised corneas. 5–8 Dorzolamide is a potentinhibitor of thecytosolic carbonicanhydrase isoenzyme (CA) II, and thecorneal endothelium contains CA II and thecytosolic CA I, which play a major role in keeping the cornea relativel ydehydrated. Dorzolamide has high activity against CA II and low activity against CA I, and thus, it has the potentialto interfere with the pumping function of the corneal endothelium, which could theoretically lead to corneal edema. 7–9 The central cornealthickness (CCT) has beenused as an indirectindicator of theendothelial function. Some inves- tigators have reported thatthere was a slight but significant increase in CCT in eyes treated with dorzolamide. 9–11 Another way to measure theendothelial function invivo is to measure the intrastromal corneal pressure (ICP), formerly known as cornealimbibition pressure, whichhas a negative value under physiologic conditions. 12–14 The amount of negative pressure in thecorneal stroma is likely to correlate with theendothelial function. 12 Theaim of thisstudy was to evaluate if treatment with topical dorzolamideaffects the ICP in rabbit corneas invivo. MATERIALS AND METHOD S Experiments were performed in eyes of male New Zealand rabbits (2.5–3.5 kg). Theanimals in thisstudy were treated according to thecurrent regulations on experimentation and animal protection used for experimentation and other scientific purposes of the Government of Spain Received for publication January 12, 2008; revision received June 24, 2008; accepted July 31, 2008. From the *Hospital Universitario Prı ´ncipe de Asturias, Alcala ´ de Henares, Madrid, Spain; †VISSUM Hospital Oftalmolo ´ gicode Madrid, Madrid, Spain; ‡Universidadde Alcala ´ , Alcala ´ de Henares, Madrid, Spain; §VISSUM Hospital Oftalmolo ´ gico de Alicante, Alicante, Spain; { Universidad Miguel Herna ´ ndez, Alicante, Spain; and k Lipshitz Eye Center, T el A viv, Israel. Supported in part by Grant number 3-2005 from Fundacio ´ n para la Investigacio ´ n Biome ´ dica del Hospital Universitario Prı ´ncipe de Asturias. Reprints: Gema Bolı ´var de Miguel, C/Jose Marı ´a Pereda, 10 2 D, C.P . 28806, Alcala ´ de Henares, Madrid, Spain (e-mail: gemabolivardemiguel@ yahoo.es). Copyright 2009 by Lippincott Williams & Wilkins 206 Corne a Vol ume 28 , Number 2 , F ebruary 2009 Copyright © 2008 Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.