M. Muraine

Paradoxical adverse events of anti-tumour necrosis factor therapy for spondyloarthropathies: a retrospective study

OBJECTIVES Several paradoxical adverse events (PAEs), e.g. IBDs, acute anterior uveitis (AAU) and psoriasis, have been described in patients taking anti-TNF drugs. This retrospective study aimed to describe the different PAEs that have occurred in a population of SpA patients treated with anti-TNF drugs, and to determine whether they are drug specific. METHODS Since 2000, we have followed 296 patients with SpA [198 AS, 21 SpA associated with IBD (9 ulcerative colitis, 12 Crohns disease) and 77 psoriatic arthritis] treated with at least one anti-TNF drug (infliximab, etanercept or adalimumab), and 112 SpA patients treated only with conventional DMARDs who served as controls. Considering the cumulative time of exposure to each anti-TNF agent, the frequencies of new-onset PAEs in exposed patients were calculated. RESULTS Respective cumulative exposure times were 287, 290 and 62 patient-years for infliximab, etanercept and adalimumab. We observed the following PAEs: five psoriasis (three under infliximab and one with etanercept or adalimumab), three AAU (1/100 patient-years, all under etanercept) and four IBD (three under etanercept and one under infliximab). There was no significant association among any of these PAEs and a specific anti-TNF agent; nor significant difference in the overall PAEs among patients receiving anti-TNF drugs or controls (P = 0.303), the latter experiencing two psoriasis and three AAU. CONCLUSIONS Undesirable side effects--IBD, AAU and psoriasis--may appear with anti-TNF drugs. Even if they are, a priori, paradoxical, no evidence supports any PAEs to be anti-TNF agent-specific in SpA.

Long-term results of penetrating keratoplasty. A 10-year-plus retrospective study.

BackgroundThe aim of this study was to retrospectively analyse the outcome of a series of grafted patients over a period of more than 10 years and to determine their long-term survival probability.MethodsThe records of 89 patients who had 103 grafts performed in 97 eyes were analysed. Mean follow-up was 12.8 years (range 10–17 years). Life table analysis (Kaplan–Meier) was used to evaluate the graft survival of the total population and of different groups.ResultsEighteen out of 89 patients (20.2%) had died. At the last visit before their death, 10 of the 21 grafts in those patients were still clear. Graft survival rates after 1, 2, 5 and 10 years were 79%, 73%, 59% and 50%; the rate at the end of follow-up was 47%. Survival rate at the end of the study was 94.7% for keratoconus, 57.1% herpes keratitis, 33.3% for pseudophakic keratopathies, 28.5% for post-traumatic keratopathies and 11.1% for re-grafts. In the group of patients grafted for aphakic or pseudophakic keratopathy, 40% died during the study. In 45% of cases their grafts were clear at the time of death. Endothelial decompensation and definitive graft rejection were the main causes of failure.ConclusionsThe outcome of keratoplasty is progressively getting worse with time in pseudophakic or traumatic keratopathies whereas survival rates are still stable from 10 to 17 years in grafts performed after keratoconus or herpetic keratitis.

Predictive visual outcome after macula-off retinal detachment surgery using optical coherence tomography.

Purpose: To determine whether preoperative optical coherence tomography (OCT) is useful in predicting postoperative visual outcome for patients with primary macula-off rhegmatogenous retinal detachment (RD). Methods: This prospective study included 20 nonconsecutive eyes with macula-off RD and successful reattachment of the retina. Preoperative 5-mm OCT was performed through the center of the fovea. The relationship among preoperative OCT findings, main preoperative clinical variables, and final postoperative visual acuity was statistically analyzed. Results: Final postoperative visual acuity was negatively correlated with three preoperative OCT variables: height of RD at the central fovea (r =0.79; P < 0.001), distance from the central fovea to the nearest undetached retina (r = 0.75; P < 0.00051), and, to a lesser degree, extent of structural changes in the detached retina (r = 0.48; P = 0.03). Preoperative visual acuity was the only clinical variable statistically correlated with final postoperative visual acuity in this study (r = 0.55; P = 0.01). Using multivariate logistic regression analyses, the structure of the detached retina combined with the distance from the central fovea to the nearest undetached retina, as determined with OCT, was highly correlated with final postoperative visual acuity (r = 0.82; P < 0.000051). Conclusion: Preoperative macular analysis with OCT may help to predict visual outcome for patients with macula-off RD.

Endophthalmitis After Intravitreal Injections: Incidence, Presentation, Management, and Visual Outcome

PURPOSE To report the incidence and characteristics of endophthalmitis after intravitreal injections of anti-vascular endothelial growth factor agents or corticosteroids and to describe the clinical and bacteriologic characteristics, management, and outcome of these eyes with acute endophthalmitis in France. DESIGN Retrospective, nationwide multicenter case series. METHODS From January 2, 2008 to June 30, 2013, a total of 316,576 intravitreal injections from 25 French ophthalmic centers were included. For each center, the number of intravitreal injections was determined using billing codes and the injection protocol was recorded. A registry and hospital records were reviewed to identify patients treated for endophthalmitis after injection during the same time period. The main outcome measures were the incidence of clinical endophthalmitis and visual acuity of endophthalmitis cases. RESULTS During the study period, 65 cases of presumed endophthalmitis were found, giving an overall incidence of 0.021% (2.1 in 10,000 injections) (95% confidence interval [CI], 0.016%-0.026%). The median number of days from injection to presentation was 4 [1-26] days. The most common symptom was vision loss. Bacterial identification was achieved in 43.4%. The most frequent pathogens were gram-positive bacteria (91.3%), including coagulase-negative Staphylococcus in 78.3%. Neither the interval between injection and presentation for endophthalmitis nor the clinical signs differentiated culture-positive from culture-negative cases. In multivariate analysis, the use of a disposable conjunctival mould assist device and the use of prophylaxis with an antibiotic or antiseptic were significantly associated with an increased incidence of endophthalmitis (P = .001). The majority of patients had worse visual acuity after 3 months of follow-up when compared with acuity before endophthalmitis. CONCLUSIONS The incidence of presumed endophthalmitis after intravitreal injections of anti-vascular endothelial growth factors or corticosteroids was low and the prognosis poor. Prevention and management remain challenging. It remains to be determined whether the findings of this study are relevant for other countries using different techniques for intravitreal injections.

Novel Technique for the Preparation of Corneal Grafts for Descemet Membrane Endothelial Keratoplasty

PURPOSE To report a simple novel technique to facilitate preparation of Descemet membrane grafts for Descemet membrane endothelial keratoplasty (DMEK). DESIGN Laboratory investigation and retrospective, single-center, consecutive case series. METHODS Preparation of the endothelial graft is performed on an artificial anterior chamber, endothelial side up. After an incomplete circular superficial trephination, we describe a simple technique using a 27 gauge cannula to detach the Descemet membrane (DM). Endothelial cell density (ECD) was measured before dissection on 12 human corneas for research and 3 days after storage in organ culture. Histologic and electron microscopy analysis were performed. A DMEK was performed in 50 patients with Fuchs dystrophy. Visual acuity and ECD were evaluated 2 and 6 months after surgery. RESULTS ECD was 2765 ± 256 cells/mm(2) on corneas for research before dissection and 2651 ± 305 cells/mm(2) after 3 days in organ culture (P < .01). Histologic and electronic sections confirm that the cleavage was between DM and posterior stroma. Clinically, preparation of 2 corneas from a single donor was unsuccessful; 48 corneas were clear at 2 months and 47 at 6 months. At 2 months 77% of the patients had recovered a visual acuity of at least 20/30. At 6 months, 91.5% of the patients had a visual acuity of at least 20/30. ECD was 2656 ± 28 cells/mm(2) (range: 2450-3100 cells/mm(2)) preoperatively, 1797 ± 41 cells/mm(2) (range: 1100-2700 cells/mm(2)) at 2 months, and 1658 ± 43 cells/mm(2) (range: 900-2600 cells/mm(2)) at 6 months. CONCLUSION We report here a reliable and efficient technique for the preparation of pure Descemet membrane grafts.

Vision-related function after scleral lens fitting in ocular complications of Stevens-Johnson syndrome and toxic epidermal necrolysis.

PURPOSE To describe the therapeutic benefits of scleral lenses in the management of severe ocular surface disease attributable to toxic epidermal necrolysis (TEN) and Stevens-Johnson syndrome (SJS). DESIGN Retrospective study. METHODS Clinical records of 39 patients (67 eyes) fitted with scleral lenses for refractory ocular surface disease attributable to SJS or TEN were reviewed. To assess vision-specific quality of life, each patient completed the Ocular Surface Disease Index (OSDI) questionnaire and the National Eye Institute Visual Function Questionnaire (NEI VFQ-25). Slit-lamp examination was performed at regular intervals to detect side effects. Main outcome measures were best-corrected visual acuity (VA) and OSDI and NEI VFQ-25 composite score before and 6 months after scleral lens fitting. RESULTS The mean age was 35.8 +/- 13.9 years. Scleral lens fitting failed in 3 patients. The mean follow-up was 33.3 +/- 17.6 months. Among fitted patients, VA in the better eye (36 patients, 36 eyes) progressed from 0.73 to 0.50 logarithm of the minimum angle of resolution (P = .0001) 6 months after scleral lens placement. The mean OSDI improved from 76.9 +/- 22.8 to 37.1 +/- 26.7 (P = .0001). Thirty-two NEI VFQ-25 composite scores were available. The mean NEI VFQ-25 composite score improved from 25.1 +/- 16.8 to 67.4 +/- 22.1 (P = .0001). No serious adverse events attributable to the scleral lenses occurred. CONCLUSIONS Scleral lens use appears to be efficient and safe for visual rehabilitation of refractory ocular surface disease attributable to TEN and SJS.

Topical treatment with a new matrix therapy agent (RGTA) for the treatment of corneal neurotrophic ulcers.

PURPOSE Neurotrophic keratopathy is a degenerative disease of the corneal epithelium resulting from impaired corneal innervation, possibly leading to perforation. We aimed to assess the efficacy and tolerance of a new matrix therapy agent (RGTA, Cacicol20), mimicking heparan sulfates, for the management of neurotrophic keratopathy. METHODS We carried out an uncontrolled, prospective, single-center clinical study on 11 patients (11 eyes) with severe corneal neurotrophic ulcers, despite the use of preservative-free artificial tears, for 15 days. Patients were treated with RGTA eye drops, instilled at a dosage of one drop in the morning, on alternate days. Evolution and follow-up during treatment were evaluated by slit-lamp examination, photography, fluorescein-dye testing, tests of corneal sensitivity, and best corrected visual acuity. The main outcome measures for each patient were healing of the corneal surface and best corrected visual acuity before and after RGTA therapy. RESULTS Eight patients displayed complete corneal healing after a mean period of 8.7 weeks (range; 1 to 22 weeks). Mean ulcer area decreased significantly, from 11.12% to 6.37% (P = 0.048) in the first week, and to 1.56% (P = 0.005) at 1 month. Treatment failure was observed in three cases, requiring amniotic membrane transplantation in two patients and penetrating keratoplasty in one patient. At the end of the study, none of the patients displayed significant improvement in visual acuity. There were no systemic or local side effects of treatment. CONCLUSIONS RGTA seems to be a potentially useful, alternative, noninvasive therapeutic approach in neurotrophic keratopathy management. However, randomized studies are necessary.

Results of surgery on macular holes that develop after rhegmatogenous retinal detachment

Aims: To evaluate the characterics and surgical prognosis of macular holes that develop after rhegmatogenous retinal detachment repair. Design: Retrospective, interventional, consecutive case series. Methods: The case records of nine patients who developed a new full-thickness macular hole after prior RD repair were reviewed over 6 years. Optical coherence tomography (OCT) confirmed these holes. They were offered surgical repair with a median follow-up of 13.3 months (1–63 months). Main outcomes included preoperative vitreo-macular status, OCT evaluation and postoperative visual acuity. Results: 1007 eyes underwent surgery for prior retinal detachment between August 1999 and September 2005. Nine eyes developed a full-thickness macular hole (prevalence 0.9%): five developed after scleral buckling surgery, one after pneumatic retinopexy and three after primary vitrectomy. The mean time to macular hole diagnosis after RD was 2.9 months (0.5–18). All patients underwent macular hole surgery by the same surgeon. At 1 month, macular hole repair was noticed in eight eyes. In this group, visual acuity at a median of 11.9 months of follow-up was 20/125 (20/400 – 20/63). Three eyes had an improvement of more than three Snellen lines. Conclusions: Macular holes developing after RD repair is a rare complication (less than 1%). Its physiopathological mechanisms are not well known. Conventional macular hole surgery including pars plana vitrectomy, inconstant internal limiting membrane delamination and long-acting gas tamponade seems to achieve to macular reattachment (89%). The visual outcome seems conditioned by the macular status noticed during the RD.

The interview with the donor's family before postmortem cornea procurement.

Purpose. Asking the family of a deceased patient to consider eye donation is one of the most difficult aspects of the donation process. The aim of this prospective study was to describe the content of interviews with the families of potential donors and to analyze their reactions to improve the process of eye donation. Methods. We consecutively met with 151 families of suitable corneal donors at the Rouen University Hospital. All interviews with donor families were analyzed using a preestablished questionnaire. Results. In only 17.9% of cases was the family aware of the potential donors last will. In 77.7% of these cases, the patient wished to donate. Procurement rate was 71.5%. This acceptance was mostly facilitated by the awareness and motivation of the hospital staff, the experience of the physician, and the 13.3-h period of time allowed after the donors death. The commitment on the part of the ophthalmologist to carry out optimal anatomical restoration was a very important point for 32% of families who accepted donation. Twenty-one percent of families asked for a delay for reflection. This delay helped to obtain a positive response in 72.7% of cases and even sometimes helped families to reconsider a previously negative position (14% of initial refusals). Conclusion. We demonstrate that a high positive response (71.5%) can be obtained from the donors family when a trained and motivated group manages the post-mortem cornea donation request.

In vivo confocal microscopic evaluation of corneal changes in chronic Stevens-Johnson syndrome and toxic epidermal necrolysis.

Purpose: To describe corneal changes visible on in vivo confocal microscopy, in patients with debilitating ocular sequelae because of toxic epidermal necrolysis (TEN) or Stevens-Johnson syndrome (SJS). Patients and Methods: Forty-one eyes of 25 consecutive patients suffering from chronic TEN or SJS were studied using in vivo confocal microscopy. Results: Severe dry eye syndrome with no associated limbal stem cell deficiency (25 eyes, 16 patients, 61%) was the most frequent clinical pattern. Limbal stem cell deficiency was noted in 16 eyes (12 patients, 39%). Three patients had asymmetric disease. Confocal microscopy showed a consistent change in the superficial epithelial cells in both clinical presentations. Patients with dry eye syndrome had frequent pathological nerve damages, and the presence of dendritic cells was prevalent (65%). Inflammatory cells were observed in a large number in 4 of the 12 patients presenting neovascularization of the cornea. Conclusions: The corneas of patients with chronic ocular sequelae linked to SJS and TEN present a number of abnormalities. In vivo confocal microscopy is a potentially useful tool for therapeutic indications and for follow-up of the debilitating chronic ocular problems associated with these diseases.