From the William and Anna Goldberg Glaucoma Service, Wills Eye Institute, Jefferson Medical College, Philadelphia, Pennsylvania.
The authors have no financial or proprietary interest in the materials presented herein.
Address correspondence to George L. Spaeth, MD, 840 Walnut Street, Suite 1110, Philadelphia, PA 19107.
Nanophthalmos is a rare, potentially devastating ophthalmic entity, with a high incidence of severe glaucoma.1 Because glaucomatous nanophthalmic eyes often respond poorly to intraocular surgery, control of the condition with medication is a high priority. We report a case of uncontrolled glaucoma in both nanophthalmic eyes of one patient that, after successive surgical complications in one of the eyes, had the intra ocular pressure (IOP) controlled in the fellow eye by only one type of medication, dorzolamide.
A 29-year-old woman was referred for consideration for uncontrolled glaucoma. She was previously diagnosed with nanophthalmos (axial length 18 mm in both eyes) and angle-closure glaucoma. Best-corrected visual acuity was 20/40 in the right eye and 20/60 in the left eye. IOP was in the range of 45 mm Hg in both eyes on timolol 0.5% and dipivefrin 0.1% in both eyes. The IOP had not fallen in response to pilocarpine 2%, latanoprost 0.005% or brimonidine 0.2% used alone or in combination. The patient was of child bearing age and wished to become pregnant. Therefore, it was elected not to use a systemic carbonic anhydrase inhibitor.
The anterior chambers were shallow with steep bowing of the irides. The pupils were minimally reactive; there was no afferent defect. Peripheral anterior synechiae (PAS) closed approximately 70% of each angle; the remainder of each angle was appositionally closed. Bilateral laser iridotomies were performed, but the angles opened only minimally between the areas of PAS and the IOP remained unchanged. Trabeculectomy with scleral windows was performed in the left eye. Postoperatively, the eye developed an aqueous misdirection syndrome, which did not respond to medical therapy; ultimately, lens extraction and vitrectomy were performed. This was followed by the development of cystoid macular edema. Final best-corrected visual acuity was 20/200 in the left eye with an IOP of 17 mm Hg. The right eye remained at 40 to 45 mm Hg on timolol 0.5% and dipivefrin 0.1%.
Dorzolamide hydrochloride, which was available for investigational use only, was obtained from the manufacturer with permission for compassionate use in this case. The IOP in the right eye fell to 15 mm Hg on dorzolamide twice daily. After 1 year of use, during which time the IOP remained at 15 mm Hg, the probability that dorzolamide was not responsible for the low IOP was considered. The medication was stopped and the IOP rose into the 40’s. Upon resumption of the medication twice daily, the IOP fell again to 15 mm Hg. The frequency of the medication was then reduced to once daily and the IOP remained at 15 mm Hg. A diurnal curve of IOP (measuring IOP at 8 a.m., 12 p.m., and 5 p.m.) showed that the IOP was at all measured times 15 mm Hg on dorzolamide once daily.
Dorzolamide hydrochloride is an effective medication in the reduction of IOP. In patients with glaucoma, the use of one drop of dorzolamide 2% three times daily results in an average IOP reduction of 18 to 22% with a duration of action of 8 hours.2 The “short” duration is the reason why the drug is approved for use as a “three times a day” drop. In the present case, the use of one drop of dorzolamide 2% caused a 30% reduction of IOP from 45 to 15 mm Hg; this effect was sustained for longer than 24 hours in this patient. Tolerance to its effect did not seem to develop as one drop of dorzolamide daily continued to control the IOP at 15 mm Hg years later. Possible explanations for this include hypersensitive cellular receptors to the drug and chronic low-grade choroidal effusion.
Dorzolamide can cause a choroidal detachment.3 This may be more common in eyes which have undergone filtration surgery in the past.4 The choroidal detachment may be due to hypotony caused by dorzolamide, or may perhaps be an idiosyncratic reaction to a sulfa-containing agent. Choroidal effusion is not a reasonable explanation in the present case; no effusion was visible clinically or with the ultrasound biomicroscopy and B-scan ultrasonography.
The fact that the patient reported here has nanophthalmos raises the possibility that the unusual response to dorzolamide could be related to the nanophthalmos. Nanophthalmos is a form of pure microphthalmos resulting from developmental arrest of the globe after closure of the embryonic fissure. It usually affects both eyes and may be inherited in an autosomal-dominant, autosomal-recessive or sporadic fashion.5 Nanophthalmic eyes tend to develop angle-closure glaucoma by the fourth to sixth decade due to progressive shallowing of the anterior chamber and narrowing of the angle.6
The mechanism of angle closure may be multifactorial and includes crowding of the anterior chamber secondary to high lens:eye volume ratio, where the “normal” size lens is too large for the abnormally reduced intraocular volume. This disparity then causes progressive PAS formation from physical displacement of the iris against the trabecular meshwork, perhaps made worse by relative pupillary block causing iridolenticular contact. Anterior chamber angles can also be closed by physical displacement of peripheral iris by anteriorly rotated ciliary processes when nanophthalmos presents with annular ciliochoroidal effusion and ciliary body detachment. Uveal effusion can induce relative pupillary block by relaxing the zonular apparatus, allowing anterior displacement of the crystalline lens and increasing iridolenticular contact. The choroidal effusion that can occur in nanophthalmos is presumably related to the thick and abnormal sclera found in these patients, which may impede vortex vein drainage and also may reduce transscleral flow of fluid from the eye.7 In the present case, no choroidal effusion was present. It appears probable that the large fall in the IOP was not related to the patient having nanophthalmos.
In summary, we report a case of angle-closure glaucoma, which had an unusually great and prolonged reduction of IOP (from 45 to 15 mm Hg lasting over 24 hours for 10 years) secondary to the use of dorzolamide once daily. The explanation for this is unclear.
- Singh OS, Simmons RJ, Brockhurst RJ, Trempe CL. Nanophthalmos: A Perspective on Identification and Therapy. Ophthalmology. 1982;89:1006–1012.
- Pfeiffer N. Dorzolamide: Development and Clinical Application of a Topical Carbonic Anhydrase Inhibitor. Surv Ophthalmol. 1997Sep–Oct; 42(2):137–151. doi:10.1016/S0039-6257(97)00053-2 [CrossRef]
- Goldberg S, Gallily R, Bishara S, Blumenthal EZ. Dorzolamide-induced Choroidal Detachment in a Surgically Untreated Eye. Am J Ophthalmol. 2004Aug; 138(2):285–286. doi:10.1016/j.ajo.2004.02.070 [CrossRef]
- Fineman MS, Katz LJ, Wilson RP. Topical Dorzolamide-induced Hypotony and Ciliochoroidal Detachment in Patients with Previous Filtration Surgery. Arch Ophthalmol. 1996Aug; 114(8):1031–1032.
- Duke-Elder S. Anomalies in the size of the eye. In Duke-Elder S, ed. System of Ophthalmology, vol. 3, pt 2. St Louis: CV Mosby; 1964: 488.
- Kimbrough RL, Trempe CS, Brockhurst RJ, Simmons RJ. Angle-closure Glaucoma in Nanophthalmos. Am J Ophthalmol. 1979; 88:572–579.
- Burgoyne C. Nanophthalmia and Chronic Angle-Closure Glaucoma. J Glaucoma. 2002; 11:525–528. doi:10.1097/00061198-200212000-00013 [CrossRef]