Abnormal retinal thickness in patients with mild cognitive impairment and Alzheimer's disease.

In Alzheimer's disease (AD), brain lesions are marked by severe neuronal loss and retinal degeneration was previously mentioned in affected patients. Mild cognitive impairment (MCI) is a clinical syndrome that could be an early phase of AD. In this study, using optical coherence tomography (OCT), the retinal nerve fiber layer (RNFL) thickness was assessed in patients with mild AD, moderate to severe AD, amnestic MCI and control subjects. The results show that RNFL thickness is statistically reduced in patients with MCI, mild AD or moderate to severe AD compared to controls. In addition, no statistical difference was found between the results in MCI patients and mild AD patients. The RNFL seems to be involved early during the course of amnestic MCI and OCT tests could be carried out in patients with cognitive troubles.

The use of impression cytology in the follow-up of severe ocular burns.

AIMS: To evaluate by impression cytology (IC) the expression of the MHC class II inflammatory marker HLA-DR by the conjunctival epithelium, the cytological modifications of the conjunctival surface according to the Nelson's classification, and the eventual correlation between the two after severe ocular burns. METHODS: A total of 24 patients (24 eyes) who presented with severe ocular burns underwent IC. We compared them with 18 healthy eyes. HLA-DR expression was studied by flow cytometry as well as the conjunctival histology evaluated with the Nelson's classification from 2-24 months after the onset of burns. RESULTS: There was a significant upregulation of the expression of HLA-DR in eyes with burns compared to the healthy population at 2 months (p<0.001), 6 months (p<0.001), 12 months (p = 0.019), 18 months (p = 0.0171) and 24 months (p = 0.01766). A significant difference was found between the Nelson grade in the pathological population and those of the healthy population at 2 months (p = 0.0157). HLA-DR upregulation was significantly correlated with the Nelson's grades between 2 months (r = 0.69, p<0.0001) and 6 months (r = 0.61, p = 0.0001). CONCLUSION: The IC technique can act as a useful tool for following-up ocular surface inflammation after severe ocular burns.

Ultrasound biomicroscopy study of the Verisyse aphakic intraocular lens combined with penetrating keratoplasty in pseudophakic bullous keratopathy.

PURPOSE: To evaluate anterior segment modifications after penetrating keratoplasty (PKP), previous anterior chamber intraocular lens (IOL) removal, and Verisyse IOL (AMO) implantation over the iris or under the iris for the treatment of pseudophakic bullous keratopathy (PBK) using ultrasound biomicroscopy. SETTING: Department of Ophthalmology, Poitiers University Hospital, Poitiers, France. METHODS: A prospective randomized comparative case series included 27 patients (27 eyes) with PBK who had PKP and implantation of a Verisyse VRSA54 aphakic IOL. The IOL was implanted over the iris in 13 patients (Group A) and under the iris in a reversed position in 14 patients (Group B). Ultrasound biomicroscopy scans 6 months after surgery measured central anterior chamber depth (ACD), iris thickness (IT), distance of the haptics from the corneal endothelium (CED), distance of the haptics from the ciliary body (CBD), angle opening distance (AOD) 500 mum from the scleral spur (AOD500) and the iridocorneal angle theta on the 4 o'clock meridian lines (AOD3; AOD9; AOD12; AOD6/theta12, theta6, theta3, theta9). RESULTS: No significant difference was found in IT, CBD, or AOD12 between Group A and Group B (P >.05). In Group B, the mean ACD was deeper by approximately 55% (P = .008); CED3 was larger by 69% (P = .0162), CED9 by 80% (P = .0128), AOD3 by 57% (P = .0309), AOD9 by 140% (P = .0057), and AOD6 by 44% (P = .0399); and theta3 was wider by 52% (P = .046), theta9 by 123% (P = .0068), theta12 by 50% (P = .0492), and theta6 by 81% (P = .0237). CONCLUSION: Ultrasound biomicroscopy showed that in eyes that had PKP with Verisyse IOL enclavation to the posterior plane of the iris, which involved posterior translation of the iridal plane, the ACD was significantly deeper and the CED and AOD were significantly larger than in eyes with anterior enclavation of the IOL.

Amniotic membrane transplantation in severe bacterial keratitis.

PURPOSE: To determine whether a combination of early amniotic membrane transplantation (AMT) and early topical corticosteroid treatment could be a safe adjuvant therapy during antibacterial treatment in severe bacterial keratitis (BK) for relieving pain, avoiding iatrogenic epithelial toxicity, and allowing earlier use of topical steroids. METHODS: In a prospective noncomparative case series, 12 patients with severe microscopically-proven BK were treated with immediate maximal topical antibiotics followed by AMT at 48 hours (single-layer epithelial side-down or multilayer epithelial side-up), plus topical steroid treatment at 72 hours. Pain relief (NRS-11 numeric rating pain scale) and the corneal epithelium healing were measured. RESULTS: The follow-up rate was 7.5 person-months, with AMT performed once in 2 patients and twice in 10 patients with BK caused by Pseudomonas aeruginosa (5), Klebsiella pneumoniae (1), Moraxella cattharalis (1), Staphylococcus aureus (1), Staphylococcus epidermidis (2), or Streptococcus pneumoniae (1). A significant decrease in the pain score was noted from the admission day (median, 8; range, 7-10) to shortly after AMT (at day 3: median, 2; range, 1-3). Epithelial healing was achieved between 8 and 45 days (mean, 25.5 +/- 9.7 days). Neither perforation nor neovascularization was observed. CONCLUSIONS: Early AMT combined with topical corticosteroid in severe BK provides immediate pain relief and allows epithelial healing.

Penetrating keratoplasty combined with posterior Artisan iris-fixated intraocular lens implantation.

PURPOSE: To present a new surgical technique combining penetrating keratoplasty and open-sky posterior iris fixation of the Artisan iris-claw intraocular lens (IOL) for treatment of pseudophakic bullous keratopathy in a case series of five patients. METHODS: A graft diameter of 8.25 mm was chosen. The formerly implanted angle-supported IOL was removed. The IOL was enclosed, entrapping a fraction of the mid-peripheral iris within the haptics whilst being held firmly with the implantation forceps. The corneal button was sutured to the recipient bed with 10-0 nylon sutures. A specular microscope was used for making an endothelial cell count. Patients underwent an ultrasound biomicroscope (UBM) scan before and 6 months after surgery and postoperative macular oedema was assessed by optical coherence tomography (OCT). The minimum follow-up was 12 months. RESULTS: Visual acuity (VA) improved in all five cases (mean best corrected VA was 0.4 postoperatively versus 1.28 preoperatively). No complications were noted. The mean endothelial cell density obtained after 1 year was 1508 cells/mm(2). The UBM study showed a deep anterior chamber and an open iridocorneal angle of 360 degrees in all cases. CONCLUSION: The implantation of the Artisan device behind the iris better preserves the anatomy of the anterior segment with respect to the iridocorneal angle.

H244R VSX1 is associated with selective cone ON bipolar cell dysfunction and macular degeneration in a PPCD family.

PURPOSE: To elucidate the retinal dysfunction and the molecular basis of posterior polymorphous corneal dystrophy (PPCD) associated with macular dystrophy, both inherited in a dominant manner through a three-generation family. METHODS: Ophthalmologic examinations including slit lamp examination, visual acuity tests, fundus visualization by scanning laser ophthalmoscopy, fluorescein angiography, color vision tests, electro-oculography, photopic and scotopic electroretinography (ERG) according to the International Society for Clinical Electrophysiology of Vision (ISCEV) protocols, and oscillatory potential (OP) recordings were conducted on affected family members. Corneal button from one affected patient was examined by transmission electron microscopy. All exons and intron-exon boundaries of the VSX1 and the COL8A2 genes were amplified by polymerase chain reaction and sequenced. RESULTS: The presence of endothelial cells that have epithelial-like features with multiple layers, desmosomal junctions, and microvillous projections supports the diagnosis of PPCD. Sequence analysis indicated that the H244R variant in the VSX1 segregated with corneal and macular disease phenotypes in this family. Electrophysiologic studies indicated normal scotopic ERG findings, decreased amplitude of the photopic b-wave, photopic OP2 and OP3 barely recordable with a preserved OP4 amplitude, and variably decreased 30-Hz flicker amplitude. CONCLUSIONS: The human VSX1 is required for cone ON bipolar cell function but not for rod and cone OFF bipolar cells, giving a unique example of such a selective heritable retinal defect in humans. Furthermore, the authors provide the first clinical support for a new alternative role of VSX1 in cone biology, probably similar to that proposed for its goldfish ortholog during retinal differentiation.

Optic neuropathy in refractory neurosarcoidosis treated with TNF-alpha antagonist.

CASE REPORT: To report a rare case of optic neuropathy in refractory neurosarcoidosis treated with tumour necrosis factor-alpha antagonist (infliximab) perfusion. A 41-year-old man with diabetes presented with an abrupt, painless, unilateral visual loss. Thoracic computed tomography disclosed mediastinal lymphadenopathy, and evidence from histopathology confirmed sarcoidosis. COMMENTS: Corticosteroids alone and with immunosuppressive agents failed to suppress the active disease. Alternative therapy of infliximab perfusions resulted in disease remission and relative visual improvement, and this treatment may warrant further clinical studies.

Recurrence of keratoconus characteristics: a clinical and histologic follow-up analysis of donor grafts.

PURPOSE: To report on clinical corneal topography, histopathologic analysis, and fine structure findings in failed grafts after penetrating keratoplasty (PK) for keratoconus (KC). DESIGN: Retrospective, consecutive, interventional case series with histologic and clinical correlation. PARTICIPANTS: Twelve corneal buttons were obtained from consecutive patients undergoing repeated PK 10 to 28 years after the initial PK for KC. The indication for regrafting was endothelial deficiency in seven cases, irreversible immune graft rejection in two cases, and corneal ectasia in three cases. METHODS: Removed corneal buttons were examined by light and transmission electron microscopy. A potential correlation between the clinical and videokeratoscopic findings and the microscopic structural observations was analyzed. RESULTS: Preoperative simulated keratometry measured by TMS-1 (Tomey, New York, NY) or EyeSys CAS (EyeSys Technology, Houston, TX) ranged from 49.8 to 66.1 diopters. A pattern compatible with KC characteristics was observed in all cases. Fine structure analysis revealed Bowman's layer disruption or folds and stromal deposits in all corneal buttons. However, central corneal thinning was not present in any of the removed buttons. CONCLUSIONS: Structure changes compatible with the diagnosis of KC were observed in all donor buttons many years after PK on KC recipients. Recurrence of the KC characteristics may result from graft repopulation by recipients' keratocytes, aging of the grafted tissue, or both.

Truncating mutations in the carbohydrate sulfotransferase 6 gene (CHST6) result in macular corneal dystrophy.

PURPOSE: Identification of mutations in the CHST6 gene in 15 patients from 11 unrelated families affected with recessive macular corneal dystrophy (MCD). METHODS: Genomic DNA was extracted from peripheral blood leukocytes of the affected patients and their healthy family members, and the mutational status of the CHST6 gene was determined for each patient by a PCR-sequencing approach. Serum concentrations of antigenic keratan sulfate for each proband were determined by ELISA. RESULTS: ELISA indicated that all affected patients, except one, were of MCD type I or IA. Fourteen distinct mutations were identified within the CHST6 coding region: 2 nonsense, 2 frameshift, and 10 missense. Of these, 12 were novel, and a nonsense mutation in the homozygous state is reported for the first time. CONCLUSIONS: These molecular results in French patients with MCD combined with those reported in previous studies indicated CHST6 mutational heterogeneity. The characterization herein of nonsense mutations is in keeping with the fact that MCD results from loss of function of the CHST6 protein product.

Phototherapeutic keratectomy for BIGH3-linked corneal dystrophy recurring after penetrating keratoplasty.

PURPOSE: To determine visual results and report side effects and complications after phototherapeutic keratectomy (PTK) for BIGH3-linked corneal dystrophy recurring after penetrating keratoplasty. DESIGN: Retrospective noncomparative case series. PARTICIPANTS: Forty-two excimer laser PTK procedures were performed in 42 eyes of 29 patients with BIGH3-linked corneal dystrophies. Genetic status of all patients was determined and allowed us to assess an unambiguous diagnosis. Preoperative diagnoses included LCDIIIA/A546T (1 eye), R124 l+DT125-DE126 (4 eyes), GICD/R555W (14 eyes), LCDI/R124C (6 eyes), SGD/R124 l (16 eyes), and CDBII/R555Q (1 eye). INTERVENTION: Two excimer lasers (Summit Excimed UV 200, Summit Technology, Waltham, MA and Nidek EC 5000, Nidek, Inc., Gamagori, Japan) were used to perform all PTKs. Indications for performing PTK after a graft were severe decrease of the best-corrected visual acuity (BCVA) related to recurrent corneal deposits and/or painful recurrent epithelial erosions. MAIN OUTCOME MEASURES: Preoperative and postoperative BCVA were analyzed, significant recurrences after treatment were noted, and postoperative complications were recorded. RESULTS: Mean preoperative BCVA was 0.2 +/- 0.12 in the decimal chart, mean postoperative BCVA was 0.52 +/- 0.16 with a mean follow-up of 3.13 +/- 1.77 years (range, 0.3-6.65 years). Visual acuity was significantly improved after surgery (P < 0.05). The magnitude of the change in visual acuity was dependent on the mutation (P < 0.001). Seven symptomatic recurrences were observed. One regressive graft rejection and 4 cases of severe postoperative haze were observed. No other complications were noted. CONCLUSIONS: PTK is a simple, safe, and efficient technique for the treatment of recurrent corneal dystrophies; in many cases it prevents or delays the major incumbent problems of repeated grafting.

Retinal angioma in a patient with Cowden disease.

PURPOSE: To report a rare case of ocular localization of Cowden disease. DESIGN: Case report. METHODS: A 50-year-old woman with a history of multiple tumors was diagnosed with Cowden disease. A PTEN gene mutation was found. Visual acuity of the left eye had decreased 2 years before diagnosis. RESULTS: Visual acuity was 20/20 in the right eye and 20/200 in the left eye. Right eye fundus examination showed an epiretinal membrane associated with a peripheral and temporal inferior angiomatous lesion. Treatment consisted of cryoapplication and surgical removal of the epiretinal membrane after central vitrectomy. Although the anatomic result was satisfactory, the patient's visual acuity remained unchanged. CONCLUSIONS: Hamartomatous ocular lesions have been described in Cowden disease. We are unaware, however, of such retinal angiomatous lesions in patients with PTEN gene mutations.

Clinical outcome of eight BIGH3-linked corneal dystrophies.

OBJECTIVE: To determine whether the mutational pattern of BIGH3-linked corneal dystrophies (CDs) can accurately predict the clinical course of the disease and be helpful in planning adequate surgical treatment. DESIGN: Retrospective noncomparative case series. PARTICIPANTS: Chart review of 73 patients (110 eyes) with recently confirmed BIGH3 mutations who underwent a penetrating keratoplasty (PK) from 1978 through 1999. Diagnoses included Thiel-Benhke CD (TBCD/R555Q) (13 eyes), classic granular CD (CGCD/R555W) (28 eyes), superficial variant of granular dystrophy (SVGD/R124 l) (27 eyes), lattice CD type I (LCDI/R124C) (20 eyes), Avellino CD (ACD/R124H) (2 eyes), H626R-lattice dystrophy (LCD/H626R) (6 eyes), and two novel dystrophies: a French variant of granular dystrophy (FVGD/R124 l+DT125-DE126) (9 eyes) and a French lattice CD type IIIA (LCDIIIA/A546T) (5 eyes). METHODS: The mutation of the BIGH3 gene was characterized for all patients. Clinical data were reviewed for each patient, and included age at first PK and elapsed time before significant recurrence (as defined by a severe decrease in best-corrected visual acuity related to recurrent deposits in the graft). MAIN OUTCOME MEASURES: Mean age at first PK and delay before a significant recurrence. RESULTS: Mutational pattern was highly correlated with the clinical course of each dystrophy. According to the genetic mutation, two groups with different prognosis were identified. Group 1 was defined by the presence of the FVGD/R124 l+DT125-DE126 and SVGD/R124 l mutations and was characterized by the early need for treatment and early recurrence of deposits. Group 2 was molecularly defined by the presence of any of the following mutations: LCDI/R124C, CGCD/R555W, LCDIIIA/A546T, TBCD/R555Q, and LCD/H626R. In group 2, mean age at first treatment was older, and delay before a significant recurrence was longer as compared with group 1 (P = 0.0001). CONCLUSIONS: These results demonstrate that there is a direct correlation between the molecular defect and the clinical course of BIGH3-linked CDs. They also indicate that molecular characterization of the genetic defect will help predict and design adequate surgical treatment for patients with ambiguous clinical diagnosis.