RESUMO
Daratumumab, an anti-CD38 monoclonal antibody, is worldwide approved for treatment of newly diagnosed and relapsed/refractory multiple myeloma (MM) patients and is available as intravenous or subcutaneous formulations. Intravenous daratumumab is associated with frequent infusion-related reactions, while eye complications, especially refractive shifts, are very rare, with only previously reported cases. Here, we described a rare case of multi-refractory MM who developed transient myopic shift during intravenous daratumumab infusion successfully treated only with cycloplegic collyrium not requiring infusion rate lowering or drug discontinuation. This conservative therapeutic approach allowed termination of induction therapy and autologous hematopoietic stem-cell transplantation resulting in durable complete remission.
Assuntos
Antineoplásicos , Mieloma Múltiplo , Humanos , Mieloma Múltiplo/tratamento farmacológico , Antineoplásicos/uso terapêutico , Anticorpos Monoclonais/efeitos adversos , Administração Intravenosa , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêuticoRESUMO
The purpose of the study was to determine the decrease in pachymetry of very thin corneas with advanced keratoconus due to corneal compaction from the ultraviolet-A (UV-A) irradiation phase of transepithelial (epi-on) cross-linking. Twenty removed corneal buttons were obtained from patients who underwent penetrating keratoplasty for advanced keratoconus. Removed corneal buttons selected from among the post-surgical specimens for this study had intact epithelium, no scarring or surgical cautery, endothelial cell density >2500 cells/mm2, and average pachymetry over the measured points of below 400 µm. Corneas were mounted in a Franz chamber. Each epithelial surface was soaked in isotonic riboflavin and D-alpha-tocopheryl polyethylene glycol 1000 succinate (Ribocross® IROMED Group, Italy) for 15 min. Pachymetry was measured at three points over both the shielded and unshielded corneal halves for each corneal button. Surfaces were then washed in saline to remove the Ribocross®. Shields from UV-A irradiation over half of each cornea were then fixed to stand 5 mm above the test corneas. UV-A irradiation using the custom fast cross-linking (CF-CXL) protocol was then performed for the typical 10 ± 1.5 min, for a total energy of 1.08 ± 0.6 J/cm2 after which pachymetry was re-measured. The average percent change in pachymetry was -0.43% ± 0.38% (maximum -1.06%) in the shielded half. Pachymetry change was -6.2% ± 2.2% (maximum 12%) in the cross-linked halves. In conclusion, we estimate that the change in corneal thickness from corneal compaction due to the cross-linking reaction itself was -5.8% ± 2.2%. Scanning electron microscopy of cross-linked corneal segments showed stromal fiber contraction.
Assuntos
Substância Própria/efeitos dos fármacos , Reagentes de Ligações Cruzadas , Ceratocone/tratamento farmacológico , Fármacos Fotossensibilizantes/farmacologia , Riboflavina/farmacologia , Vitaminas/farmacologia , alfa-Tocoferol/farmacologia , Paquimetria Corneana , Substância Própria/patologia , Substância Própria/ultraestrutura , Humanos , Ceratocone/patologia , Microscopia Eletrônica de Varredura , Tamanho do Órgão , Raios UltravioletaRESUMO
PURPOSE: To improve the safety, reproducibility, and depth of effect of corneal cross-linking with the ultraviolet A (UV-A) exposure time and fluence customized according to the corneal thickness. METHODS: Twelve human corneas were used for the experimental protocol. They were soaked using a transepithelial (EPI-ON) technique using riboflavin with the permeation enhancer vitamin E-tocopheryl polyethylene glycol succinate. The corneas were then placed on microscope slides and irradiated at 3 mW/cm for 30 minutes. The UV-A output parameters were measured to build a new equation describing the time-dependent loss of endothelial protection induced by riboflavin during cross-linking, as well as a pachymetry-dependent and exposure time-dependent prescription for input UV-A fluence. The proposed equation was used to establish graphs prescribing the maximum UV-A fluence input versus exposure time that always maintains corneal endothelium exposure below toxicity limits. RESULTS: Analysis modifying the Lambert-Beer law for riboflavin oxidation leads to graphs of the maximum safe level of UV-A radiation fluence versus the time applied and thickness of the treated cornea. These graphs prescribe UV-A fluence levels below 1.8 mW/cm for corneas of thickness 540 µm down to 1.2 mW/cm for corneas of thickness 350 µm. Irradiation times are typically below 15 minutes. CONCLUSIONS: The experimental and mathematical analyses establish the basis for graphs that prescribe maximum safe fluence and UV-A exposure time for corneas of different thicknesses. Because this clinically tested protocol specifies a corneal surface clear of shielding riboflavin on the corneal surface during UV-A irradiation, it allows for shorter UV-A irradiation time and lower fluence than in the Dresden protocol.
Assuntos
Córnea/efeitos dos fármacos , Córnea/efeitos da radiação , Reagentes de Ligações Cruzadas/farmacologia , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/uso terapêutico , Riboflavina/farmacologia , Raios Ultravioleta , Colágeno/efeitos dos fármacos , Colágeno/efeitos da radiação , Humanos , Modelos Teóricos , Fotoquimioterapia/efeitos adversos , Reprodutibilidade dos TestesRESUMO
PURPOSE: To report the clinical outcomes with 24-month follow-up of transepithelial cross-linking using a combination of a D-alpha-tocopheryl polyethylene-glycol 1000 succinate (vitamin E-TPGS)-enhanced riboflavin solution and abbreviated low fluence UV-A treatment. METHODS: In a nonrandomized clinical trial, 25 corneas of 19 patients with topographically proven, progressive, mild to moderate keratoconus over the previous 6 months were cross-linked, and all patients were examined at 1, 3, 6, 12, and 24 months. The treatments were performed using a patented solution of riboflavin and vitamin E-TPGS, topically applied for 15 minutes, followed by two 5-minute UV-A treatments with separate doses both at fluence below 3 mW/cm(2) that were based on preoperative central pachymetry. RESULTS: During the 6-month pretreatment observation, the average Kmax increased by +1.99 ± 0.29 D (diopter). Postoperatively, the average Kmax decreased, changing by -0.55 ± 0.94 D, by -0.88 ± 1.02 D and by -1.01 ± 1.22 D at 6, 12, and 24 months. Postoperatively, Kmax decreased in 19, 20, and 20 of the 25 eyes at 6 months, 12 months, and 24 months, respectively. Refractive cylinder was decreased by 3 months postoperatively and afterward, changing by -1.35 ± 0.69 D at 24 months. Best spectacle-corrected visual acuity (BSCVA) improved at 6, 12, and 24 months, including an improvement of -0.19 ± 0.13 logarithm of the minimum angle of resolution units at 24 months. There was no reduction in endothelial cell count. No corneal abrasions occurred, and no bandage contact lenses or prescription analgesics were used during postoperative recovery. CONCLUSIONS: Transepithelial cross-linking using the riboflavin-vitamin E solution and brief, low-dose, pachymetry-dependent UV-A treatment safely stopped keratoconus progression.
Assuntos
Reagentes de Ligações Cruzadas , Ceratocone/tratamento farmacológico , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/uso terapêutico , Riboflavina/uso terapêutico , Raios Ultravioleta , Vitamina E/análogos & derivados , Adulto , Colágeno/metabolismo , Substância Própria/metabolismo , Combinação de Medicamentos , Feminino , Humanos , Ceratocone/metabolismo , Ceratocone/fisiopatologia , Masculino , Soluções Oftálmicas , Polietilenoglicóis/uso terapêutico , Estudos Prospectivos , Dosagem Radioterapêutica , Resultado do Tratamento , Acuidade Visual/fisiologia , Vitamina E/uso terapêutico , Adulto JovemRESUMO
To evaluate the efficiency and safety of iontophoretic transepithelial corneal crosslinking in pediatric patients with progressive keratoconus underwent general or topical anesthesia in 18 months follow-up. 13 patients (13 eyes) diagnosed with progressive keratoconus underwent corneal CXL with iontophoresis (I-CXL). Riboflavin solution was administered by iontophoresis for 5 min, and then UV-A irradiation (10 mW/cm) was performed for 9 min. Preoperative and post-operative visits at 1, 6, 12, and 18 months assessed the following parameters: uncorrected visual acuity (UCVA), best-corrected visual acuity (BCVA), slit-lamp biomicroscopy, corneal topography, optical tomography, and pachymetry with Pentacam (Oculus Optikgeräte GmbH, Wetzlar, Germany), endothelial biomicroscopy (Konan Specular Microscope; Konan Medical, Inc., Hyogo, Japan). The paired Student t test was used to compare data during the follow-up. 10 males and 3 females with a mean age of 15.4 ± 1.7 years (range 11-18 years) were included. The results showed a stabilization of the refractive UCVA and BCVA as early as the first post-operative month, with a slight improvement over time. The Kmax remained stable throughout follow-up (p = 0.04). Transepithelial collagen crosslinking by iontophoresis, unlike other transepithelial techniques seems to halt pediatric keratoconus progression over 18 months. This is the second study evaluating CXL with iontophoresis in pediatric patients with progressive keratoconus with 18 months of follow-up using two different ways of anesthesia.