Clinical spectrum of eye malformations in four patients with Mowat-Wilson syndrome.

Mowat-Wilson syndrome (MWS) is a rare genetic syndrome characterized by a specific facial gestalt, intellectual deficiency, Hirschsprung disease and multiple congenital anomalies. Heterozygous mutations or deletions in the zinc finger E-box-binding homeobox2 gene (ZEB2) cause MWS. ZEB2 encodes for Smad-interacting protein 1, a transcriptional co-repressor involved in TGF-beta and BMP pathways and is strongly expressed in early stages of development in mice. Eye abnormalities have rarely been described in patients with this syndrome. Herein, we describe four patients (two males and two females; mean age 7 years) with MWS and eye malformations. Ocular anomalies included, iris/retinal colobomas, atrophy or absence of the optic nerve, hyphema, and deep refraction troubles, sometimes with severe visual consequences. All eye malformations were asymmetric and often unilateral and all eye segments were affected, similarly to the nine MWS cases with ophthalmological malformations previously reported (iris/chorioretinal/optic disc coloboma, optic nerve atrophy, retinal epithelium atrophy, cataract, and korectopia). In human embryo, ZEB2 is expressed in lens and neural retina. Using the present report and data from the literature, we set out to determine whether or not the presence of eye manifestations could be due to specific type or location of mutations. We concluded that the presence of eye malformations, although a rare feature in MWS, should be considered as a part of the clinical spectrum of the condition.

[Persistent foveal retinal detachment after successful rhegmatogenous retinal detachment surgery by scleral buckling]. / Persistance de liquide sous-rétinien maculaire après traitement d'un décollement de rétine rhegmatogène par cryothérapie-indentation.

We report the case of a phakic patient with late visual recovery after successful surgery of macula-off retinal detachment, using the scleral buckling procedure. Visual acuity remained low because of the persistence of subfoveal fluid despite the reattachment of peripheral retina. The amount of subfoveal fluid decreased slowly and final visual acuity finally recovered. We used optical coherence tomography (OCT) to quantify the remaining subfoveal fluid. Persistence of submacular fluid can explain late visual recovery after surgical treatment of retinal detachment.

Trefoil factor family 1, MUC5AC and human leucocyte antigen-DR expression by conjunctival cells in patients with glaucoma treated with chronic drugs: could these markers predict the success of glaucoma surgery?

AIMS: To evaluate conjunctival expression of trefoil factor family (TFF)1, MUC5AC and human leucocyte antigen (HLA)-DR in patients with glaucoma treated with topical drugs, and to determine whether these parameters can predict the outcome of glaucoma surgery. METHODS: 77 conjunctival impression cytology specimens were collected from 77 patients with glaucoma (66 receiving drops with preservative and 11 treated with preservative-free drops) and 43 controls. TFF1, MUC5AC and HLA-DR expression was analysed using flow cytometry. Trabeculectomy was performed in 56 patients; success was defined as an intraocular pressure (IOP) < or =15 mm Hg without any IOP-lowering drug at 6 months. RESULTS: The expression of TFF1, MUC5AC and HLA-DR was significantly higher in patients than in controls (p = 0.01, 0.05 and 0.004, respectively). A higher expression of MUC5AC was found in patients treated with preserved drops than in those receiving unpreserved drops (p = 0.04). A higher MUC5AC expression and a lower HLA-DR expression was observed in successful glaucoma surgeries than in failures. CONCLUSIONS: TFF1 and MUC5AC secretions are probably a response to mild ocular surface changes caused by long-term use of topical treatment. Their increased expression could be a predicting factor of further successful glaucoma surgery.

[Study of ocular surface involvement in diabetic patients]. / Etude des atteintes de la surface oculaire chez les patients diabétiques.

INTRODUCTION: Diabetes mellitus leads to microvascular complications and altered basement membranes, which are partly responsible for ocular complications. Corneal nerve impairment is involved in ocular surface disease as well. We examined the possible relation between ocular surface signs and retinal or neuronal degenerative complications due to diabetes. PATIENTS AND METHODS: Diabetics and control subjects were compared for corneal sensitivity and tear function parameters such as the Schirmer test, tear film break-up time (BUT), and fluorescein and lissamine green stainings. The relation of the duration of the disease, the stage of retinopathy, metabolic control (HbA1c), and diabetic peripheral neuropathy with ocular surface disorders were noted. RESULTS: Twelve healthy patients were compared to 48 diabetics. The Schirmer test value, BUT, and fluorescein and lissamine green impregnations were significantly modified in diabetics compared to controls (p<0.0001), with no relation to the duration of the disease or metabolic control. The mean corneal sensitivity was significantly lower in diabetic patients (p<0.01), diabetics with peripheral neuropathy (p=0.00008), and diabetics with preproliferative retinopathy (p=0.0003). Tear function parameters were more frequently altered in patients presenting preproliferative retinopathy and peripheral neuropathy (p<0.001). CONCLUSIONS: Diabetes can lead to ocular surface impairments with qualitative and quantitative tear disorders, all of which seem to evolve in close relation with retinopathy and peripheral neuropathy. These lacrymal and corneoconjunctival abnormalities, even if not currently mentioned by diabetic patients, can result in severe neurotrophic complications.

[Postoperative acute endophthalmitis: a prospective study. Clinical presentation, management and prognostic factors]. / Etude prospective sur les endophtalmies aiguës postopératoires. Description clinique, prise en charge facteurs de risque.

AIMS: To assess the characteristics and visual outcome of patients with acute postoperative endophthalmitis hospitalized in a referral center. MATERIALS AND METHODS: All patients suspected of having infectious endophthalmitis were included in this study. All patients were treated with the same protocol including at least intravitreal injection of antibiotics and instillation of fortified antibiotics. Symptoms, visual acuity, and slit lamp examination were recorded before treatment, at the end of hospitalization and during clinical follow-up. Treatments and biological results were also reported. For patients developing infectious endophthalmitis after cataract surgery, intraoperative management such as location of the incision, suture or sutureless incision, and material of the intraocular lens were also noted. RESULTS: Forty-one patients were included in the study over 32 months (33 patients after cataract surgery). Intraocular inflammation and a decrease in subjective visual acuity were the most frequently reported findings (90% and 94%, respectively). Ocular pain and conjunctiva injection were less frequently reported (47% and 48%, respectively). Symptoms occurred 5 days after the surgery (median); 56% of patients needed a second intravitreal injection of antibiotics. There was a significant increase in visual acuity during and after hospitalization; median final visual acuity was 4.6/10 (0.34 log MAR = 20/43); 30% of patients had less than 20/200, but 44% more than 20/40. In endophthalmitis following cataract surgery, incisions were corneal in all cases and sutured in 62% of cases. Incisions were temporal in 55% of patients. DISCUSSION: Our results are similar to those previously published for acute endophthalmitis following ocular surgery. Intravitreal antibiotic injection remains the gold standard on the management of acute postoperative endophthalmitis.

[Treating severe dry eye syndromes with autologous serum]. / Traitement des syndromes secs graves par sérum autologue.

BACKGROUND: Dry eye syndrome with tear deficiency can be improved with artificial tears, which can be associated with topical anti-inflammatory agents. Autologous serum can provide the ocular surface with beneficial growth factors and vitamins. PATIENTS AND METHODS: Twenty-one patients suffering from severe dry eye due to Sjögren's syndrome were treated with 20% autologous serum for 2 Months. The Schirmer I test, break-up time, and fluorescein and lissamine green stainings were performed before and after treatment. Subjective complaints such as burning, foreign body sensation, dryness and photophobia were assessed by a questionnaire as well as a face score reflecting the current condition of patients' eyes. RESULTS: Lissamine green and fluorescein scores improved significantly as well as subjective symptoms of burning, foreign body sensation and dryness (p<0.05). The face score was significantly improved. Bacterial culture of serum delivered to the patients all remained negative. DISCUSSION: Autologous serum provides growth factors and vitamins that are useful for an altered ocular surface due to Sjögren's disease. However, some problems still remain: risk of contamination, arbitrary dilution of autologous serum, and a current lack of regulations for use of autologous serum. A close collaboration between ophthalmologists and the Etablissement Français du Sang (French Blood Bank) is mandatory because autologous serum should be considered as a useful tool to treat severe ocular surface disorders. CONCLUSION: The use of autologous serum improved symptoms and objective signs caused by severe Sjögren's syndrome. Currently, a lack of clear regulations prevents its widespread use in severe ocular surface disorders.

[A screening questionnaire for determining risk of Creuzfeldt-Jacob disease transmission during ophthalmic examination]. / Intérêt d'un questionnaire de dépistage du risque de transmission de la maladie de Creutzfeldt-Jacob en consultation d'Ophtalmologie.

INTRODUCTION: The risk of prion transmission during an ophthalmic examination concerns all ophthalmologists screening patients at risk, a procedure normally based on collecting past history and clinical data. PATIENTS AND METHODS: The authors proposed a shortened version of a questionnaire where the patient provides only the past history by answering three questions, which are then validated by the ophthalmologist. RESULTS: This procedure was proposed to 500 patients. Only five patients answered one of the questions positively, and the ophthalmologist did not use any contact device during their examination. Of these five patients, none was confirmed to be at risk for prion transmission. CONCLUSION: This questionnaire seems to be a suitable way to compensate the lack of time and reduced staff in ophthalmology, whatever the ophthalmic practice may be.

[Trefoil factor family gene and peptide expression in pterygium]. / Etude des peptides en trèfle dans le ptérygion.

PURPOSE: Trefoil factor family (TFF) peptides (formerly P-domain peptides; trefoil factor) are small (7-12 kDa) protease-resistant secreted peptides designated pS2 (or TFF1), SP (TFF2) and ITF (TFF3). Human conjunctival goblet cells (GCs) are known to synthesize TFF, but TFF expression by these cells has not been studied in pathological conditions. We quantified trefoil factor family (TFF) gene transcripts in pterygium, and we immunolocalized TFF protein. METHODS: Eleven pterygium specimens were studied, together with 19 biopsy specimens of normal human conjunctiva as controls. TFF1 (pS2), TFF2 (spasmolytic peptide) and TFF3 (intestinal trefoil factor) mRNA expression was semiquantified by means of reverse-transcription polymerase chain reaction amplification (RT-PCR). TFF1, TFF2 and TFF3 mRNA levels were determined individually, relative to beta2 microglobulin housekeeping gene mRNA (internal standard), by coamplification of the target fragments and beta2 microglobulin in the same tube. Five pterygia and five normal human conjunctival biopsy specimens were also analyzed for TFF1 and mucin (MUC5AC) protein expression by immunostaining with monoclonal antibodies. Anti-PS2 (Zymed Laboratories, San Francisco), a mouse monoclonal antibody (MAb) against the 30 C-terminal amino acids of human TFF1, and P2802 (provided by Doctor Marie-Christine Rio, Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS/INSERM, Strasbourg, France), a mouse MAb directed against a synthetic peptide corresponding to the last 28 amino acids of TFF1, were used at 1/20 dilution. A mouse monoclonal antibody directed against the peptidic core of gastric M1 mucin was used as previously described. M1 immunoreactivity is encoded by the MUC5AC gene. RESULTS: TFF1 and TFF3 mRNA was expressed in all normal conjunctival and pterygium specimens. TFF2 mRNA was not expressed by either sample type, but was expressed by the positive control (human stomach cDNA). TFF1 mRNA expression was stronger in pterygium than in controls (p=0.02). TFF3 mRNA expression was similar in the two sample types (p=0.89). TFF are coexpressed and act in concert with mucins to protect mucous epithelia and trigger wound-healing responses. Inflammation and ulceration of the gastrointestinal tract are associated with increased TFF expression. Conjunctival GCs secrete TFF in both pigs and humans. We found that TFF1 mRNA was overexpressed in pterygium relative to healthy conjunctiva, whereas the TFF1 immunostaining patterns were similar. TFF1 protein expression was confined to goblet cells. However, whereas all GCs were positive for MUC5AC, not all GC were labeled by anti-TFF1 mAbs in either normal conjunctiva or pterygium. The observed TFF1 mRNA overexpression in pterygium was not associated with abnormal TFF1 peptide localization. Increased MUC5AC protein expression would be expected in pterygium, because of increased GC density. Indeed, in conjunctival diseases such as dry-eye syndrome in which GC density is decreased, mucin secretion is also decreased. This could explain the increased expression of TFF1 mRNA in pterygium, although not all GCs expressed TFF1 protein. TFF proteins are copackaged within mucous cell granules; TFF1 preferentially colocalizes with MUC5AC, and TFF3 with MUC2. However, we found some cell granules containing MUC5AC but not TFF1. The proportion of TFF1-negative GCs was similar in pterygium and normal conjunctiva. The normal TFF3 mRNA expression in pterygium was unexpected and suggests that only GCs involved in TFF1 secretion are overrepresented in this pathological tissue. TFF2 mRNA was undetectable in both normal conjunctiva and pterygium, possibly because of its copackaging in mucous cell granules and its preferential cosecretion with MUC6, which is not expressed in the conjunctiva. CONCLUSION: As in normal conjunctiva, the TFF1 and TFF3 genes are expressed by conjunctival goblet cells in pterygium, contrary to the TFF2 gene. Only TFF1 gene expression was elevated in pterygium compared to normal conjunctiva.