Late and sustained intraocular pressure elevation related to intravitreal anti-VEGF injections: Cases requiring filtering surgery.

We report cases of delayed, sustained elevated intraocular pressure (IOP) associated with repeated intravitreal anti-VEGF injections (IVI), which ultimately resulted in the need for filtering surgery. Two of the three cases demonstrated severe IOP elevation despite maximal medical treatment following unilateral IVI and required urgent filtering surgery. Optic nerve involvement was severe in all three cases. These intravitreal injections were performed for exudative age-related macular degeneration (AMD), and the patients did not show any sign of glaucoma or ocular hypertension prior to the initiation of treatment. Elevated IOP secondary to intravitreal steroids is a well-known side effect, as is immediate transient IOP elevation associated with anti-VEGF injection. Late, sustained IOP elevation after repeated injections of anti-VEGF, described approximately ten years ago, is often underestimated. Its incidence is estimated between 2.1 % and 13 % according to studies and increases with the number of IVI (cumulative effect). The pathophysiologic process is becoming increasingly understood, and several risk factors for this chronic IOP elevation have been identified. Most often, it is a moderate IOP elevation for which topical monotherapy is sufficient, or sometimes two, three or four medications or even selective laser trabeculoplasty (SLT). However, filtering surgery may rarely be required. Our findings illustrate a little-described phenomenon: a sudden, severe, late IOP elevation in response to anti-VEGF by an "overflow" effect, requiring urgent filtering surgery.

[Late and sustained intraocular pressure elevation related to intravitreal anti-VEGF injections: Cases requiring filtering surgery (French translation of the article)]. / Hypertonie intraoculaire retardée liée aux injections intra-vitréennes répétées d'anti-VEGF : des cas nécessitant une chirurgie filtrante.

We report cases of delayed, sustained elevated intraocular pressure (IOP) associated with repeated intravitreal anti-VEGF injections (IVI), which ultimately resulted in the need for filtering surgery. Two of the three cases demonstrated severe IOP elevation despite maximal medical treatment following unilateral IVI and required urgent filtering surgery. Optic nerve involvement was severe in all three cases. These intravitreal injections were performed for exudative age-related macular degeneration (AMD), and the patients did not show any sign of glaucoma or ocular hypertension prior to the initiation of treatment. Elevated IOP secondary to intravitreal steroids is a well-known side effect, as is immediate transient IOP elevation associated with anti-VEGF injection. Late, sustained IOP elevation after repeated injections of anti-VEGF, described approximately ten years ago, is often underestimated. Its incidence is estimated between 2.1% and 13% according to studies and increases with the number of IVI (cumulative effect). The pathophysiologic process is becoming increasingly understood, and several risk factors for this chronic IOP elevation have been identified. Most often, it is a moderate IOP elevation for which topical monotherapy is sufficient, or sometimes two, three or four medications or even selective laser trabeculoplasty (SLT). However, filtering surgery may rarely be required. Our findings illustrate a little-described phenomenon: a sudden, severe, late IOP elevation in response to anti-VEGF by an "overflow" effect, requiring urgent filtering surgery.

Fibroblast growth factor (FGF) soluble receptor 1 acts as a natural inhibitor of FGF2 neurotrophic activity during retinal degeneration.

Fibroblast growth factors (FGF) 1 and 2 and their tyrosine kinase receptor (FGFR) are present throughout the adult retina. FGFs are potential mitogens, but adult retinal cells are maintained in a nonproliferative state unless the retina is damaged. Our work aims to find a modulator of FGF signaling in normal and pathological retina. We identified and sequenced a truncated FGFR1 form from rat retina generated by the use of selective polyadenylation sites. This 70-kDa form of soluble extracellular FGFR1 (SR1) was distributed mainly localized in the inner nuclear layer of the retina, whereas the full-length FGFR1 form was detected in the retinal Muller glial cells. FGF2 and FGFR1 mRNA levels greatly increased in light-induced retinal degeneration. FGFR1 was detected in the radial fibers of activated retinal Muller glial cells. In contrast, SR1 mRNA synthesis followed a biphasic pattern of down- and up-regulation, and anti-SR1 staining was intense in retinal pigmented epithelial cells. The synthesis of SR1 and FGFR1 specifically and independently regulated in normal and degenerating retina suggests that changes in the proportion of various FGFR forms may control the bioavailability of FGFs and thus their potential as neurotrophic factors. This was demonstrated in vivo during retinal degeneration when recombinant SR1 inhibited the neurotrophic activity of exogenous FGF2 and increased damaging effects of light by inhibiting endogenous FGF. This study highlights the significance of the generation of SR1 in normal and pathological conditions.

[Postoperative endophthalmitis: 2000-2002 results in the XV-XX National Ophthalmologic Hospital]. / Infections nosocomiales endoculaires au CHNO des XV-XX de 2000 à 2002.

PURPOSE: Prevention of nosocomial infection is a priority for the Infection Control Committee (ICC). Following their recommendations, the XV-XX National Ophthalmologic Hospital's ICC conducted a survey on cases of infection and we report these results for the 2000-2002 period. METHODS: During the 2000-2002 period, 21,384 programmed intraocular surgeries were done. Every day, a hygiene coordinator was informed of each bacterial or fungal laboratory test on intraocular samples and for all patients who were hospitalized for endophthalmitis. After data analysis with a referent ICC physician, resulting infection was declared postoperative nosocomial endophthalmitis. For these patients, prophylactic antibiotic use, the surgery report, and bacterial laboratory test results were reviewed. RESULTS: The overall 3-year incidence of suspected postoperative endophthalmitis after intraocular surgery was 2.0 per 1000 (42 cases). Confirmed microbiological growth was demonstrated in 19 cases (45%). For cataract surgery, the incidence was 1.0 per 1000 for acute-onset culture-proven postoperative endophthalmitis, 0.1 per 1000 for delayed culture-proven postoperative endophthalmitis, 2.1 per 1000 for acute-onset suspected postoperative endophthalmitis and 0.5 per 1000 for delayed suspected postoperative endophthalmitis. Gram-positive cocci were isolated in 77%. Twenty-one patients received systemic prophylactic antibiotics. Bacterial growth was positive in five of these 21 cases. For two cases, organisms were resistant to the prophylactic antibiotics used. CONCLUSION: Monitoring postoperative nosocomial infection is mandatory to detect incidence variation and evaluate infection control management. Prophylactic antibiotic efficacy remains to be evaluated.

[Early postoperative intraocular pressure after phacoemulsification: Normal patients versus glaucoma patients]. / Pression intraoculaire en postopératoire précoce de phakoémulsification chez le sujet normal et glaucomateux.

OBJECTIVE: To compare intraocular pressure (IOP) during the first month following cataract surgery among patients with primary open-angle glaucoma (POAG) and non-glaucomatous patients. MATERIALS AND METHODS: This longitudinal observational study included 19 glaucoma patients and 18 healthy patients scheduled for phacoemulsification with IOL implantation between December 2013 and April 2014. IOP was measured preoperatively, on the day of surgery (j0), the next day (j1), one week (j7) and one month after (M1). The usual antiglaucoma medications were continued without any modification compared to the preoperative medications. Oral treatment with a carbonic anhydrase inhibitor was initiated in the case of ocular hypertension above 30mmHg. RESULTS: IOP in glaucoma patients was 18.42 and 21.16mmHg respectively at j0 and j1 versus 12.94 and 13.78mmHg in non-glaucomatous patients. The difference was significant with P=0.05. There was also more ocular hypertension over 30mmHg in the POAG group (31.5% vs. none in the non-glaucomatous group, P<0.05). CONCLUSION: Glaucoma patients, even stabilized on topical medications, are more likely to experience IOP spikes immediately after uncomplicated cataract surgery. High risk patients should have closer monitoring with IOP measurement the day of or the day after surgery. Further studies are needed to evaluate the effectiveness of prophylactic anti-hypertensive treatment.

[Efficacy of intravitreal dexamethasone implants in macular edema excluding venous occlusions: results for a cohort of 80 patients]. / Efficacité des implants intravitréens de dexaméthasone dans l'œdème maculaire hors occlusions veineuses : résultats sur une cohorte de 80 patients.

INTRODUCTION: The intravitreal dexamethasone implant has shown efficacy in the treatment of macular edema (ME) arising after retinal venous occlusions (central or branch), and in the treatment of non-infectious uveitis. The purpose of this study was to evaluate the efficacy of this implant in the treatment of other diffuse macular edemas with an inflammatory mechanism. MATERIALS AND METHODS: We carried out a retrospective cohort study over 2 years: from January 2012 to December 2013, including all patients who received at least one injection of intravitreal dexamethasone implant, excluding venous occlusions and non-infectious uveitis. The primary study parameter was the progression of visual acuity. The study protocol had the approval of the institutional review board of the respective clinical ethics committees, and was conducted in accordance to the tenets of the Declaration of Helsinki. RESULTS: Eighty patients were included. Eighty-eight percent of patients were pseudophakic. The indications for treatment were: diabetic ME when anti-VEGF were ineffective (53%), ME after retinal detachment (RD) (22%), ME of Irvine-Gass syndrome (16%), ME after endophthalmitis (4%), macular telangiectasia (4%), ME secondary to retinitis pigmentosa (1%). The mean ETDRS visual acuity was 53.7 letters prior to injection, improving to 62.3 letters after injection (P<0.001). The average gain in visual acuity was 6.7 letters [4.53;8.84] (P<0.001) in patients treated for diabetic ME, 9.6 letters [6.1;13.1] (P<0.001) in patients with ME after RD, and 15.2 letters [10.25;20.28] (P<0.001) for Irvine-Gass syndrome. The mean duration of efficiency was 4.6 months, with a median of 3.8 months. CONCLUSION: The intravitreal dexamethasone implant appears to be an effective second-line treatment even in patients with diabetic ME after failure or in the case of contraindication of anti-VEGF. It is also effective and well tolerated in patients with ME after RD, as well as in patients with Irvine-Gass syndrome.

[Williams-Beuren syndrome: diagnosis and ocular manifestations]. / Syndrome de Williams-Beuren: diagnostic et manifestations oculaires.

A 24-year-old woman presented with a Williams-Beuren Syndrome which included a characteristic facies, cardiovascular dysfunction and neurologic troubles. Ophthalmic examination showed a stellate pattern of the iris and tortuosities of the retinal vessels. Knowledge of these ocular manifestations could help early diagnosis.

[Carbohydrate-deficient-glycoprotein syndrome and ophthalmological manifestations]. / Syndrome d'hypoglycosylation des glycoprotéines sériques et manifestations ophtalmologiques.

INTRODUCTION: Carbohydrate-deficient-glycoprotein syndromes are new described multisystemic diseases. We report here the case of a young boy who presented with CDG syndrome Ia associated with typical ocular disorders. CASE REPORT: This 18-month-old boy presented facial dysmorphism, ataxia, hypotonia and cerebellar hypoplasia. Ocular examination showed esotropia with nystagmoid movements and at fundoscopy signs of retinitis pigmentosa with foveal hypoplasia. Photopic and scotopic electroretinograms were altered. DISCUSSION: CDG syndromes are metabolic disorders which affect N-glycoprotein synthesis. Clinical manifestations are various: hypotonia, cerebellar hypoplasia, developmental delay, pericardial effusion, etc. Four variants are described; each of them is associated with particular clinical disorders and prognosis. Ocular features are frequently associated (esotropia, retinitis pigmentosa) and especially in CDG syndrome Ia. CONCLUSION: Esotropia associated with fundus alterations appearing in a multisystemic disorder requires explorations to search for CDG syndrome.

[Urrets-Zavalia syndrome]. / Syndrome d'Urrets-Zavalia.

We report four cases of Urrets-Zavalia Syndrome (fixed dilated pupil with iris atrophy) observed after penetrating keratoplasty. The precise etiology of the syndrome is uncertain and different mechanisms are reviewed. Care should be taken to avoid the use of mydriatic eye drops after penetrating keratoplasty.

[Evaluation by laser flare meter of the inflammatory response after cataract surgery]. / Evaluation par laser flare meter de la réponse inflammatoire après chirurgie de la cataracte.

PURPOSE: To prospectively evaluate use of the laser flare meter the inflammatory response after phacoemulsification with four different types of intraocular lenses. METHODS: Measurements with the Kowa laser flare meter FC-500 were done before surgery and at 1, 6 and 21 days following standard phacoemulsification with corneal incision in 157 patients. The patients were randomized in four groups to receive HSM IOL (group I), foldable acrylic IOL (group II), foldable three-piece silicone (group III), and foldable single-piece silicone (group IV). RESULTS: Overall, mean flare values were increased at D1, and decreased rapidly to normal values at D21. Intragroup analysis showed a slight increase of flare value observed in the PMMA group (p = 0.0015) and silicone monobloc group (p = 0.001) at D21 compared to D0. There was no statistical difference found between D0 and D21 in the acrylic and the silicone three pieces groups. At D1, a significant increase of flare values was observed in the PMMA (28.9 ph/ms) and silicone three pieces (28.8 ph/ms) groups, as compared to silicone monobloc group (22 ph/ms). At D21, the acrylic group had a significantly lower mean value than PMMA and silicone monobloc groups. No statistical difference was observed between acrylic and three-piece silicone at D21. CONCLUSION: This study shows that the inflammation in the four groups was very low after phacoemulsification by a corneal incision and attempts to explain the impact of the incision length on the breakdown of blood-aqueous barrier.

[Clinical evaluation of the ocular safety of Amukine 0.06% solution for local application versus povidone iodine (Bétadine) 5% solution for ocular irrigation) in preoperative antisepsis]. / Evaluation clinique de la tolérance oculaire d'Amukine 0,06% solution pour application locale versus povidone iodée (Bétadine 5% solution pour irrigation oculaire) en antisepsie pré-opératoire.

INTRODUCTION: The aim of this monocentric, randomized, comparative, open study was to evaluate the safety of Amukine 0.06% solution (an isotonic hypochloride sodium solution) versus a 5% povidone iodine solution (Bétadine 5% solution for ocular irrigation) in antisepsis before cataract surgery. MATERIAL AND METHODS: One hundred and thirteen patients, aged between 49 and 90 years, were included and split, after randomization, into two groups: one testing Amukine 0.06%, the other testing a 5% povidone iodine solution. For each group, after local anesthesia, the antiseptic procedure consisted of an antisepsis of periocular teguments followed by an eye antisepsis through the instillation of two drops of the tested product in the conjunctival fornices. The safety evaluation was performed by grading superficial punctate keratitis 24 hours after surgery (slit lamp examination after fluorescein instillation). Conjunctival hyperemia scores by examination of the bulbar conjunctiva before the first instillation, immediately before surgery, and 24 hours after surgery were also compared. RESULTS: One hundred and seven reports were analyzed. Concerning the presence of corneal superficial punctate keratitis 24 hours after surgery, mean scores were not different (0.27 for the Amukine 0.06% group and 0.38 for the povidone iodine group; p=0.27 Mann Whitney test). The observations did not show a different progression of conjunctival hyperemia depending on the treatment group (p=0.65 (immediately after application) and p=0.52 (after 24 hours); Mann Whitney test). CONCLUSION: In this study, the ocular safety of Amukine 0.06% solution was not different from a 5% povidone iodine solution. Therefore, Amukine 0.06% is a new interesting approach to surgical antisepsis in ophthalmology and an alternative in case of iodine allergy.

[Evaluation of preoperative anxiety in patients requiring glaucoma filtration surgery]. / Évaluation de l'anxiété préopératoire chez les patients nécessitant une chirurgie filtrante du glaucome.

PURPOSE: Preoperative anxiety is often expressed by patients requiring filtration surgery for their glaucoma. So far, there has been no scale for screening this group of patients for preoperative anxiety. The Amsterdam Preoperative Anxiety and Information Scale (APAIS) is a self-evaluation questionnaire which has been used in specialties other than ophthalmology and which makes it possible to identify the adult patients with a high level of preoperative anxiety over an upcoming surgical procedure. The purpose of this study is to estimate the preoperative anxiety in glaucoma patients requiring filtration surgery. METHODS: We performed a prospective study of 36 adult patients with chronic glaucoma not responding to medical treatment and who were about to undergo filtration surgery (trabeculectomy or deep sclerectomy). The APAIS questionnaire was given to the patients after discussing the indication for surgery. A global anxiety score (ranging from 4 to 20) above 10 defined patients with a high level of preoperative anxiety. We attempted to identify among these patients the factors related to filtration surgery which caused them anxiety (lack of control of intraocular pressure, risk of blindness, presence of the filtering bleb). RESULTS: In our sample of patients, we found that glaucoma was a source of anxiety. That was also true for the surgical procedure, though most patients believe that once the decision had been made, their psychological status was not modified by the upcoming procedure. DISCUSSION: The patient-clinician relationship is important in any chronic disease, all the more so in glaucoma, since this disease remains asymptomatic for a long time. When filtration surgery is necessary, the patients are going to express less preoperative anxiety if they trust their physician and if individualized information has been given to them CONCLUSION: The French version of the APAIS is a quick scale, easily completed, that can be recommended for evaluating anxiety and patients' need for information prior to filtering surgery. It is usually easier for the surgeon to find ways to reduce the patient's anxiety if a relationship of trust has been established between the two.

[Anterior chamber migration of a dexamethasone implant in a pseudophakic patient with a scleral-fixated posterior chamber intraocular lens]. / Migration d'un implant de dexaméthasone en chambre antérieure chez un patient pseudophaque porteur d'un implant de chambre postérieur suturé à la sclère.

We report the case of anterior chamber migration of a dexamethasone implant (Ozurdex(®)) in a 54-year-old woman with macular edema due to a central retinal vein occlusion. The patient had undergone complicated cataract surgery 5 years previously with a scleral-fixated posterior chamber lens implant. An uneventful intravitreal Ozurdex(®) implant injection was performed. One month later, the patient presented emergently with painless visual loss. Slit-lamp examination revealed the presence of discrete corneal edema associated with the implant in the anterior chamber. The implant was surgically removed from the anterior chamber 24 hours later with complete resolution of corneal edema.

[Visante® OCT findings of Descemet membrane detachment after refractive lensectomy: A case report]. / Aspects en OCT Visante® de décollement descémétique après lensectomie réfractive : à propos d'un cas.

Descemet membrane detachment (DMD) is a rare complication that occurs mainly after cataract surgery. We report the case of a 55-years-old woman who underwent refractive lensectomy. The Day-1 postoperative examination was unremarkable, the Day-7 examination showed corneal oedema related to DMD, which was confirmed by Visante(®) OCT. An intracameral injection of SF6 expansive gas allowed the reapplication of the membrane and the receding of corneal oedema. Through this observation, we discuss the pathogenesis of this uncommon entity and the contribution of Visante(®) OCT.

[Surgical session: neovascular glaucoma and anti-vascular endothelial growth factor treatment]. / Glaucome néovasculaire et traitement anti-angiogénique.

Recent research has shown the key role of vascular endothelial growth factor (VEGF), mainly one of its isoform, VEGF-A, in ocular pathologies involving neovascularization. New intraocular treatments targeting specifically VEGF (anti-VEGF) has been developed. These agents have revolutionized the treatment and visual prognosis of neovascular agerelated macular degeneration (AMD). Their potential for other ocular diseases, such as neovascular glaucoma, is currently under clinical investigations. We briefly review the current knowledge and clinical data, and present our clinical experience with the use of intravitreal bevacizumab in neovascular glaucoma.

[Management of ocular hypertension and chronic open-angle glaucoma by French ophthalmologists: the role of target intraocular pressure]. / Prise en charge de l'hypertonie oculaire et du glaucome chronique à angle ouvert par les ophtalmologistes français: rôle de la pression intra-oculaire cible.

PURPOSE: A low level of intraocular pressure (IOP) can reduce or even stop the progression of glaucoma. It is essential to limit conversion from ocular hypertension (OHT) to glaucoma. The IOP value that protects the visual field and the optic nerve is called target IOP. This study analyzes how French ophthalmologists determine the target IOP level. MATERIAL AND METHODS: The main objective of this prospective, multicenter national survey was to analyze the management of OHT or glaucoma patients and to evaluate the importance of target IOP in the therapeutic strategy. RESULTS: A total of 972 ophthalmologists included 11.177 patients from May 2002 to March 2004. In 68.7% of cases, the practitioner determined the target IOP level using the following methods: a target of 15 mmHg or 17 mmHg or a reduction of the IOP level in percentage (EGS guidelines). This mean target IOP ranged from 14.3 to 17.3 mmHg. DISCUSSION: The estimation of target IOP is used by the majority of French ophthalmologists. CONCLUSION: This study shows that the determination of target IOP is becoming increasingly important in the therapeutic decision and follow-up in the routine practice of French ophthalmologists.

The role of PKCzeta in NMDA-induced retinal ganglion cell death: prevention by aspirin.

Intravitreal NMDA injection has been shown to induce the excitotoxic loss of retinal cells. The retinal ganglion cell apoptosis induced by NMDA is thought to play an important role in retinal ischemia injury and NMDA-injected rat has been used as a model of neuronal loss in diseases such as glaucoma. In this experimental model, we studied the early effects of NMDA leading to the degeneration of retinal ganglion cells. PKCzeta regulates the NF-kappaB pathway in cellular responses to various stresses and we have shown that aspirin inhibits purified human PKCzeta. We therefore investigated the molecular mechanism by which retinal cells limit ocular injury following NMDA treatment. We found that the NMDA-induced apoptosis of ganglion cells was mediated, at least partly, by PKCzeta. This enzyme was activated early in the cellular response to NMDA. Prolonged activation was followed by PKCzeta cleavage, and nuclear translocation of the C-terminal region of this protein-a critical event for the survival of retinal cells. We also found that pretreatment with aspirin or the coinjection of NMDA with a specific PKCzeta inhibitor counteracted the effects of NMDA. These findings provide new insight into the role played by PKCzeta in neuronal loss in glaucoma.