Intravenous high-dose methotrexate based systemic therapy in the treatment of isolated primary vitreoretinal lymphoma: An LOC network study.

The treatment of primary vitreoretinal lymphoma (PVRL) remains controversial regarding the use of local, systemic, or combined treatments. The aim of this study was to analyze the efficacy and toxicity of intravenous high-dose methotrexate (IV HD-MTX) based systemic therapy in a uniformly treated population of PVRL patients. From a nationwide French database, we retrospectively selected 59 patients (median age: 70 years, median Karnofsky Performance Status: 90%) with isolated PVRL at diagnosis who received first-line treatment with HD-MTX between 2011 and 2018. 8/59 patients also received a local treatment. No deaths or premature discontinuations of MTX due to toxicity were reported. A complete response was obtained in 40/57 patients after chemotherapy. Before treatment, IL-10 was elevated in the aqueous humor (AH) or in the vitreous in 89% of patients. After treatment, AH IL-10 was undetectable in 87% of patients with a CR/uCR/PR and detectable in 92% of patients with PD/SD. After a median follow-up of 61 months, 42/59 (71%) patients had relapsed, including 29 isolated ocular relapses as the first relapse and a total of 22 brain relapses. The median overall survival, progression-free survival, ocular-free survival and brain-free survival were 75, 18, 29 and 73 months, respectively. IV HD-MTX based systemic therapy as a first-line treatment for isolated PVRL is feasible, with acceptable toxicity, even in an elderly population. This strategy seems efficient to prevent brain relapse with prolonged overall survival. However, the ocular relapse rate remains high. New approaches are needed to improve local control of this disease, and ocular assessment could be completed by monitoring AH IL-10.

[Benign lymphoid hyperplasia associated with HIV: An exceptional orbital location]. / Hyperplasie lymphoïde associée au VIH : une localisation orbitaire exceptionnelle.

HIV-related lymphoid hyperplasia has been exceptionally described outside lymph nodes. To our knowledge, 3 cases of nasopharyngeal localisation have been described in the literature. We report here an intracranial localisation with an important ophthalmological clinical impact. Our observation allows us to approach the differential diagnoses of intracranial lesions in the HIV-positive patient, to analyse the differential diagnoses of benign lymphoid hyperplasia and to discuss the therapeutic options.

Cytological diagnosis of vitreoretinal lymphomas: A case series.

OBJECTIVE: To assess the cytological diagnosis and follow-up of patients suffering from vitreoretinal lymphoma (VRL) diagnosed in our institution. METHODS AND RESULTS: From January 2010 to June 2017, we collected 15 patients with VRL. Twelve patients had diffuse large B-cell lymphoma (DLBCL); of these, 11 had primary central nervous system (CNS) DLBCL, one had ocular localisation of follicular lymphoma, one had extranodal NK/T-cell nasal type lymphoma and one had chronic lymphocytic leukaemia. The results of the cytological examination (cell morphology and immunocytochemistry) of the vitreous fluid were available for 9/15 VRL. The interleukin-10/-6 ratio was >1 in eight of 12 DLBCL. Molecular testing was useful in 6/15 cases (clonality evaluation or MYD88 L265P mutation testing). Eight out of 11 primary CNS DLBCL patients had CNS involvement, with 22-month progression-free survival. In our series, only two out of 11 CNS DLBCL patients died of disease after 2 and 5 years, respectively. CONCLUSIONS: The short delay to assert the diagnosis of VRL could explain the quite good prognosis in our series, which highlights the need to consider a diagnosis of DLBCL as first step. The cytological features, as a reliable way to identify VRL, must always guide the choice of techniques for further investigations given the small amount of vitreous fluid available for analysis.

Improving the cytological diagnosis of intraocular lymphoma from vitreous fluid.

AIMS: To improve the cytological diagnosis of retinal lymphoma on vitreous fluid using improved cell collection and systematic analyses. METHODS AND RESULTS: Since October 2010, we have developed and optimized in our department a method with which to perform the diagnosis of retinal lymphoma. The vitreous sample was collected in a tube containing RPMI-1640 medium, decomplemented fetal bovine serum, and gentamicin. The transport and technical steps were performed at 4°C. Systematically, cytological examination with May-Grünwald-Giemsa staining and immunocytochemistry (mainly anti-CD3, anti-CD20 and anti-CD68 antibodies) were performed on cytospins. Whenever possible, determination of B-cell clonality, flow cytometry and determination of the interleukin (IL)-10/IL-6 ratio were performed. From October 2010 to June 2013, with this optimized protocol, 38 vitreous cytological samples from 32 patients were analysed, and a final diagnosis was possible, avoiding a biopsy, in all cases except one. CONCLUSION: The preservation of vitreous fluid cells on culture medium led to the diagnosis of retinal lymphoma in 10 of 12 cases, and exclusion of this diagnosis in 26 cases. This protocol may be applied even when the delay in shipping from the surgery to the pathology departments exceeds 1 h.

[Ocular conjunctival pathology. A ten-year retrospective study in Toulouse-Rangueil University Hospital and literature review]. / Pathologie oculaire conjonctivale. Étude rétrospective sur dix ans au CHU de Toulouse-Rangueil et revue de la littérature.

Our study aim is to assess the distribution of conjunctival eye lesions received in our institution between 01/01/1999 and 16/10/2010, in order to put forward the diagnostic difficulties associated with this location and the specific terms employed for ophthalmologic pathology. Twenty-one samples were analyzed. The non-tumoral lesions accounted for more than one half (pterygium, pinguecula, epithelial cyst, foreign body). The tumoral lesions were mainly represented by naevi. The naevi were characterized in this location by the presence of intralesional epithelial cysts, which distinguished them from primary acquired melanosis and melanoma. Only one case of papilloma was observed. In one fourth of the cases, the final pathological diagnosis was different from the clinical diagnosis. It seems legitimate to recommend a pathological analysis of conjunctiva lesions systematically.

Factors associated with favorable visual outcome after surgery of clinoidal meningiomas.

BACKGROUND: The anatomical relationship between clinoidal meningiomas and the optic nerve accounts for their frequent finding on visual disturbances. The goal of the surgery is to perform complete resection and obtain visual recovery. The aim of this study is to determine the factors associated with favorable visual outcome. METHODS: We recorded clinical (including ophthalmological), imaging and surgical data of all patients operated on for clinoidal meningiomas between 2010 and 2020 in 2 French neurosurgical departments and we analyzed their impact on visual outcome. RESULTS: A total of 34 patients were included. At 3-4 months after surgery, 23 patients (68%) had favorable visual outcome. Factors associated with favorable visual outcome were duration of ophthalmologic symptoms < 6 months, preoperative visual acuity > 0.5, absence of optic atrophy, meningioma in high signal intensity on T2-weighted or FLAIR MRI, absence of optic canal involvement and absence of bone hyperostosis on pre-operative CT scan. A soft tumor and a clear brain/tumor border were intra-operative factor associated with favorable ophthalmological outcome. CONCLUSIONS: In clinoidal meningiomas, an early surgery should be performed to optimize visual improvement. Hyperintense lesion on T2-weighted/FLAIR preoperative MRI is correlated with a soft consistency which allows an easier surgery associated with a favorable visual outcome. Invasion of the optic canal and bone hyperostosis should reserve the visual prognosis.

Predictive Factors of Favorable Visual Outcomes After Surgery of Tuberculum Sellae Meningiomas: A Multicenter Retrospective Cohort Study.

BACKGROUND: Because of their proximity to the visual structures, tuberculum sellae meningiomas are frequently revealed by ophthalmologic impairment. The goal of surgery is gross total resection and improvement of visual function. The purpose of the present study was to identify the predictors of favorable visual outcomes after surgery of tuberculum sellae meningioma. METHODS: We retrospectively collected tuberculum sellae meningiomas treated at 2 neurosurgical centers from 2010 to 2020. We collected the clinical, imaging and surgical data and analyzed their effects on the visual outcome. A favorable visual outcome was defined as an increase in visual acuity of ≥0.2 point and/or an increase of >25% of the visual field or complete recovery. RESULTS: A total of 50 patients were included. At 4 months after surgery, 30 patients (60%) had experienced visual improvement. The predictors of a favorable visual outcome were a symptom duration of <6 months, preoperative visual acuity >0.5, a smaller tumor size, and tumor with T2-weighted/fluid attenuated inversion recovery hypersignal on magnetic resonance imaging. During surgery, a soft tumor and a clear brain-tumor interface were associated with favorable visual outcomes. Preoperative optic coherence tomography measurements of the retinal nerve fiber layer thickness >80 µM and ganglion cell complex thickness >70 µM were also associated with a better ophthalmologic outcome. CONCLUSIONS: In tuberculum sellae meningiomas, rapid surgical treatment must be performed to optimize vision improvement. A hyperintense lesion on T2-weighted/fluid attenuated inversion recovery magnetic resonance imaging and minor vision impairment at the initial ophthalmologic presentation might give hope for a favorable outcome. Performing optic coherence tomography measurements before surgery could clarify patients' expectations regarding their recovery.

Effects of Resistance Exercise with or without Whey Protein Supplementation on Ocular Changes after a 21-Day Head-Down Bed Rest.

Neuro-ophthalmological changes have been reported after prolonged exposure to microgravity; however, the pathophysiology remains unclear. The objectives of the present study were twofold: (1) to assess the neuro-ophthalmological impact of 21 days of head-down bed rest (HDBR) and (2) to determine the effects of resistance vibration exercise (RVE) alone or combined with nutritional supplementation (NeX). In this case, 12 healthy male subjects completed three interventions of a 21-day HDBR: a control condition without countermeasure (CON), a condition with resistance vibration exercise (RVE) comprising of squats, single leg heel and bilateral heel raises and a condition using also RVE associated with nutritional supplementation (NeX). Intraocular pressure (IOP) was assessed by applanation tonometry. Retinal nerve fiber layer thickness (RNFLT) was assessed with spectral-domain optical coherence tomography, before HDBR and between Day 2 and Day 4 after each session of HDBR. In CON condition, IOP was preserved; while in RVE and NeX conditions, IOP was increased. In CON condition, RNFLT was preserved after HDBR. RVE and NeX conditions did not have significant effects on RNFLT. This study showed that a 3-week HDBR did not induce significant ophthalmological changes. However, RVE induced an elevation in IOP after HDBR. Nutritional supplementation did not reduce or exacerbate the side effects of RVE.

Prospective Assessment of Early Proton Therapy-Induced Optic Neuropathy in Patients With Intracranial, Orbital or Sinonasal Tumors: Impact of A Standardized Ophthalmological Follow Up.

PURPOSE: Proton therapy (PT) can be a good option to achieve tumor control while reducing the probability of radiation induced toxicities compared to X-ray-based radiotherapy. However, there are still uncertainties about the effects of PT on the organs in direct contact with the irradiated volume. The aim of this prospective series was to report 6-month follow-up of clinical and functional optic neuropathy rates of patients treated by proton therapy using a standardized comprehensive optic examination. METHODS AND MATERIALS: Standardized ophthalmological examinations were performed to analyze subclinical anomalies in a systematic way before treatment and 6 months after the end of proton therapy with: Automatic visual field, Visual evoked potential (VEP) and optic coherence of tomography (OCT). RESULTS: From October 2018 to July 2020 we analyzed 81 eyes. No significant differences were found in the analysis of the clinical examination of visual functions by the radiation oncologist. However, considering VEP, the impairment was statistically significant for both fibers explored at 30'angle (p:0.007) and 60'angle (p <0.001). In patients with toxicity, the distance of the target volume from the optical pathways was more important with a p-value for 30'VEP at 0.035 and for 60'VEP at 0.039. CONCLUSIONS: These results confirm uncertainties concerning relative biological effectiveness of proton therapy, linear energy transfer appears to be more inhomogeneous especially in areas close to the target volumes. The follow-up of patients after proton therapy is not an easy process to set up but it is necessary to improve our knowledges about the biological effects of proton therapy in real life. Our study which will continue during the coming years, suggests that follow-up with in-depth examinations such as VEP as a biomarker could improve the detection of early abnormalities.

Ceramide production associated with retinal apoptosis after retinal detachment.

BACKGROUND: During retinal detachment, premature apoptosis of photoreceptors and a loss of optimally corrected visual acuity occur. We hypothesized that retinal cell death and generation of ceramide, a pro-apoptotic lipid, would progress as a function of time following experimental retinal detachment, and undertook to define the appropriate temporal window. METHODS: Unilateral retinal detachment was induced in white New Zealand rabbits by subretinal injection of sodium hyaluronate. In experimental animals, we injected sphingosine-1-P into the vitreous 2 hours before retinal detachment. Both eyes were removed on days 1, 3 and 6 for histological and biochemical examination. The number of photoreceptors was counted in section, the level of apoptosis was assessed using the TUNEL assay, and the production of ceramide was analyzed in situ with immunohistochemistry. The concentration of ceramide was also determined on retinal homogenates using a diacylglycerol kinase assay. RESULTS: We confirmed that the average number of live photoreceptors decreased gradually after retinal detachment. In eyes pre-treated with sphingosine-1-P the number of apoptotic photoreceptors was significantly lower. The proportion of apoptotic photoreceptors (14%) remained constant as a function of time in the window studied. As compared to controls, the detached retina showed intense ceramide immunostaining that was prominent in the photoreceptors, but also present to a lesser extent in other retinal layers. The total concentration of intra-retinal ceramide increased by 40% on the first day and continued augmenting through the sixth day after retinal detachment. CONCLUSIONS: Retinal apoptosis during experimental retinal detachment is associated with in vivo production of ceramide.

Silicone oil migration in the eyelid after vitrectomy for retinal detachment.

PURPOSE: To report a case of silicone oil intrusion in the upper eyelid, expressed by ptosis occurrence 19 years after surgery. METHODS: Vitrectomy followed by transscleral subretinal fluid drainage and silicone oil tamponade was performed on a 57-year-old man for retinal detachment. Nineteen years later, the patient was referred for mobile subcutaneous lumps of the upper right eyelid. Preoperative examination showed total invasion of the eyelid by silicone oil, as confirmed by pathology. RESULTS: Silicone oil leak developed through the transscleral drainage lumen and worsened with ocular hypertension. We assume that ptosis was induced by the weight of inflammatory tissue and consequently the development of a lymphoedema. CONCLUSION: We report a case of silicone ptosis. Two concomitant factors induced oil leakage: the puncture site and postoperative hypertonia.

Peribulbar anaesthesia using a combination of lidocaine, bupivocaine and clonidine in vitreoretinal surgery.

PURPOSE: The efficacy and safety of peribulbar anaesthesia was assessed using a combination of lidocaine, bupivacaine and clonidine during eye surgery. METHODS: We prospectively studied 100 vitreo-retinal surgical procedures performed by several surgeons. The exclusion criteria included age below 30 years and, axial length of the orbit above 28 mm. Peribulbar was performed using Hamilton's technique. A mixed anaesthetic solution of equal quantity of lidocaine 2% and bupivacaine 0.5% with clonidine (1 mg/kg) was injected. Patients received a mean volume of 14.5 ml +/- 3.5 of the mixture. Akinesia and analgesia were assessed 15 minutes later by the surgeon. Whenever required, supplemental lidocaine 2% (3 ml) by sub-Tenon infiltration was added by the surgeon. Supplemental injections were given only to patients who failed to develop analgesia. RESULTS: The mean age of patients (male 52%, female 48%) was 66 years +/- 10 (mean +/- SD, range 44-90). The 100 surgical procedures were made up of vitrectomy +/- gas +/- silicone oil (22/100), vitrectomy and lensectomy (6/100), vitrectomy and epiretinal membrane +/- laser coagulation +/- gas +/- silicone oil (35/100), scleral buckling or encircling +/- gas (36/100), and cryosurgery +/- gas (1/100). Analgesia was adequate throughout surgery without any supplementation in 85% of cases and with a sub-Tenon infiltration in 99%. Akinesia was complete in 84%, mild in 12% and absent in 4% of cases. The sub-Tenon injection was performed in 15% of cases. Three patients (3%) were agitated during surgery. No neurologic or cardiac complication was seen. In one patient, the systolic blood pressure decreased from 170 to 110 mmHg, 30 minutes after the institution of the peribulbar block. CONCLUSION: Our results show that peribulbar anaesthesia in the proposed mixture offers excellent analgesia in 85% of patients, and in 99% of the patients when supplemented by a subtenon injection. The current mixture of lidocaine, bupivacaine and clonidine is an excellent alternative to the previously used mixture etidocaine, bupivacaine and hyaluronidase for vitreoretinal surgery. However, a randomized controlled clinical trial is needed to prove the efficacy and safety of these results.

Sphingosine-1 phosphate prevents ethanol-induced corneal epithelial apoptosis.

BACKGROUND: Apoptosis is a programmed cell death in multicellular organisms, found in a wide variety of conditions, including inflammatory process, everywhere in the body, including the cornea and conjunctiva. AIM: To evaluate the effect of a new topical formulation of sphingosine-1 phosphate on preventing apoptosis of the corneal epithelium. SETTING: Medical University. MATERIALS AND METHODS: We tested several formulations suitable for topical application. Twenty-five rabbits were distributed among five groups. Group 1 comprised the controls. In Group 2, 20% ethanol was applied topically for 20 seconds; in Group 3, 50 µM topical sphingosine-1 phosphate was applied 2 hours prior to 20% ethanol application. In Group 4, 200 µM topical sphingosine-1 phosphate was applied 2 hours before the 20% ethanol application. In Group 5, only 200 µM topical sphingosine-1 phosphate was applied. Apoptosis was evaluated using the terminal deoxynucleotidyl transferase biotin-dUTP Nick End Labeling (TUNEL) assay. Pairwise comparisons were performed using t-tests with Scheffe's correction. Data were analyzed using STATA 9.0 statistical software. RESULTS: A suspension of sphingosine-1 phosphate in the presence of Montanox 80 was stable and could be formulated without sonication. Epithelial apoptosis was detected only in Groups 2 and 3. CONCLUSION: Sphingosine-1 phosphate can prevent ethanol-induced apoptosis in the corneal epithelium of rabbits.

Sphingosine-1 phosphate prevents ethanol-induced corneal epithelial apoptosis.

Background: Apoptosis is a programmed cell death in multicellular organisms, found in a wide variety of conditions, including inflammatory process, everywhere in the body, including the cornea and conjunctiva. Aim: To evaluate the effect of a new topical formulation of sphingosine-1 phosphate on preventing apoptosis of the corneal epithelium. Setting: Medical University. Materials and Methods: We tested several formulations suitable for topical application. Twenty-five rabbits were distributed among five groups. Group 1 comprised the controls. In Group 2, 20% ethanol was applied topically for 20 seconds; in Group 3, 50 μM topical sphingosine-1 phosphate was applied 2 hours prior to 20% ethanol application. In Group 4, 200 μM topical sphingosine-1 phosphate was applied 2 hours before the 20% ethanol application. In Group 5, only 200 μM topical sphingosine-1 phosphate was applied. Apoptosis was evaluated using the terminal deoxynucleotidyl transferase biotin-dUTP Nick End Labeling (TUNEL) assay. Pairwise comparisons were performed using t-tests with Scheffe's correction. Data were analyzed using STATA 9.0 statistical software. Results: A suspension of sphingosine-1 phosphate in the presence of Montanox 80 was stable and could be formulated without sonication. Epithelial apoptosis was detected only in Groups 2 and 3. Conclusion: Sphingosine-1 phosphate can prevent ethanol-induced apoptosis in the corneal epithelium of rabbits.

Sub-Tenon infiltration or classical analgesic drugs to relieve postoperative pain.

BACKGROUND: In a prospective randomized double-blind study, the analgesic effect produced by sub-Tenon infiltration was compared with classic analgesic drugs in patients scheduled for posterior segment surgery under general anaesthesia. METHODS: One hundred patients were randomized into two groups of 50. One group received sub-Tenon infiltration (group 1) with 3 mL of bupivacaine 0.50% by the surgeon before the end of the surgery and the other (group 2) received only classical analgesic drugs postoperatively. A visual analogue scale (VAS) (graded from 1 to 10) was used to assess pain. For both groups, when VAS was between 1 and 3 paracetamol (3 g/24 h) associated with ketoprofen (200 mg/24 h) was given; between 3 and 6 nalbuphine (0.2 mg/kg slowly intravenously repeated every 4 h if necessary) was given; and over 6 morphine was given. Morphine 1 mg was injected every 2 min until VAS below 3 was obtained. RESULTS: All patients in group 2 (control) experienced pain in the recovery room period; however, no patient in group 1 required analgesic drugs in the first 6 h after the sub-Tenon infiltration. In the recovery room period, the VAS pain score in patients who received sub-Tenon infiltration (group 1) was 0.6 +/- 1.3 (mean +/- SD) compared to 3.4 +/- 2.2 in group 2. The difference was statistically significant (P = 0.000001). All patients in group 2 asked for analgesic drugs in the recovery room, some of whom required morphine. Despite the administration of drugs the pain score was statistically higher in group 2. Between the end of the recovery room period and the 6th hour, the VAS pain score in group 1 was statistically lower. From the 6th until the 24th hour, the pain score was not statistically significantly different between the groups. Regarding consumption of analgesic drugs from the recovery room until the 24th hour, the consumption of level 1 analgesic drugs (paracetamol, ketoprofen) and level 3 (morphine) was statistically lower in group 1 (P = 0.0009). The difference was not significant for level 2, probably because the number of patients was not sufficient. CONCLUSION: Sub-Tenon infiltration with 3 mL of bupivacaine 0.50% offers excellent postoperative analgesia for about 6 h and is an excellent alternative to classical drugs. Furthermore, it is highly reliable and safe.