title: Rebound macular edema following oral acetazolamide therapy for juvenile X-linked retinoschisis in an Italian family.
abstract: BACKGROUND
  Juvenile X-linked retinoschisis (RS1, OMIM: 312700) is a hereditary vitreoretinal dystrophy characterized by bilateral foveal schisis and, in half of the patients, splitting through the nerve fiber layer in the peripheral retina. In the first decade of life, patients usually develop a decrease in visual acuity. Long-term visual outcomes can be poor due to the limited number of known successful treatments.
  
  
  OBJECTIVE
  The purposes of this study were to present, for the first time, a p.Arg197Cys missense mutation in theRS1gene (OMIM: 300839) in a four-generation Italian family with RS1 and to examine the clinical response to the treatment with acetazolamide tablets alone or in combination with dorzolamide eye drops as assessed by spectral-domain optical coherence tomography (SD-OCT).
  
  
  METHODS
  Eleven individuals, including two brothers with RS1 (patients 1 and 2), underwent a full medical history examination and a comprehensive ocular assessment that involved SD-OCT, fluorescein angiography, electroretinography and DNA analysis. Each RS1 patient received oral acetazolamide (375 mg daily) during the first three months. Thereafter, patient 1 continued only with dorzolamide eyedrops three times a day for a period of three months, while patient 2 spontaneously stopped both medications.
  
  
  RESULTS
  Sequence analysis of theRS1gene identified a hemizygous c.589C>T (p.Arg197Cys) missense mutation in exon 6, which has not been previously reported in an Italian family. A different response to the medical therapy was observed in the four eyes of the two affected brothers hemizygous for this abnormality. Of note, after acetazolamide interruption, a rebound effect on cystoid macular edema reduced the beneficial effects of the initial therapy for RS1 from p.Arg197Cys mutation. Indeed, a minimal rebound effect on cystoid macular edema, and an improvement in visual acuity, was observed in patient 1 during the six months of treatment. Conversely, in patient 2, an initial improvement in cystoid macular edema was not associated with visual acuity changes, followed by a marked rebound effect.
  
  
  CONCLUSIONS
  This study showed that the sequential use of acetazolamide tablets and dorzolamide eye drops should be considered and studied further as a possible treatment for macular edema and visual impairment in patients with RS1 from a hemizygous p.Arg197Cys mutation.
authors.affiliation: Department of Surgical Sciences, Eye Clinic, University of Cagliari, Cagliari, Italy.
authors.forename: Maria Silvana
authors.initials: MS
authors.lastname: Galantuomo
authors.affiliation: Department of Surgical Sciences, Eye Clinic, University of Cagliari, Cagliari, Italy.
authors.forename: Maurizio
authors.initials: M
authors.lastname: Fossarello
authors.affiliation: Department of Surgical Sciences, Eye Clinic, University of Cagliari, Cagliari, Italy.
authors.forename: Alberto
authors.initials: A
authors.lastname: Cuccu
authors.affiliation: Department of Surgical Sciences, Eye Clinic, University of Cagliari, Cagliari, Italy.
authors.forename: Roberta
authors.initials: R
authors.lastname: Farci
authors.affiliation: Department of Ophthalmology, Faculty of Medicine, Justus-Liebig-University, Giessen, Germany.
authors.forename: Markus N
authors.initials: MN
authors.lastname: Preising
authors.affiliation: Department of Ophthalmology, Faculty of Medicine, Justus-Liebig-University, Giessen, Germany.
authors.forename: Birgit
authors.initials: B
authors.lastname: Lorenz
authors.affiliation: Department of Surgical Sciences, Eye Clinic, University of Cagliari, Cagliari, Italy.
authors.forename: Pietro Emanuele
authors.initials: PE
authors.lastname: Napoli
keywords: cystoid macular edema; foveal zone thickness; juvenile X-linked retinoschisis; macular schisis; oral acetazolamide; topical dorzolamide