Rapid Onset of Retinal Toxicity From High-Dose Hydroxychloroquine Given for Cancer Therapy
AMERICAN JOURNAL OF OPHTHALMOLOGY
2015; 160 (4): 799-805
Rapid Onset of Retinal Toxicity From High-Dose Hydroxychloroquine Given for Cancer Therapy.
American journal of ophthalmology
2015; 160 (4): 799-805 e1
Restoration of Retinal Structure and Function after Selective Photocoagulation
JOURNAL OF NEUROSCIENCE
2013; 33 (16): 6800-6808
To report rapid onset of retinal toxicity in a series of patients followed on high-dose (1000 mg daily) hydroxychloroquine during an oncologic clinical trial studying hydroxychloroquine with erlotinib for non-small cell lung cancer.Retrospective observational case series.Ophthalmic surveillance was performed on patients in a multicenter clinical trial testing high-dose (1000 mg daily) hydroxychloroquine for advanced non-small cell lung cancer. The US Food & Drug Administration-recommended screening protocol included only visual acuity testing, dilated fundus examination, Amsler grid testing, and color vision testing. In patients seen at Stanford, additional sensitive screening procedures were added at the discretion of the retinal physician: high-resolution spectral-domain optical coherence tomography (OCT), fundus autofluorescence (FAF) imaging, Humphrey visual field (HVF) testing, and multifocal electroretinography (mfERG).Out of the 7 patients having exposure of at least 6 months, 2 developed retinal toxicity (at 11 and 17 months of exposure). Damage was identified by OCT imaging, mfERG testing, and, in 1 case, visual field testing. Fundus autofluorescence imaging remained normal. Neither patient had symptomatic visual acuity loss.These cases show that high doses of hydroxychloroquine can initiate the development of retinal toxicity within 1-2 years. Although synergy with erlotinib is theoretically possible, there are no prior reports of erlotinib-associated retinal toxicity despite over a decade of use in oncology. These results also suggest that sensitive retinal screening tests should be added to ongoing and future clinical trials involving high-dose hydroxychloroquine to improve safety monitoring and preservation of vision.
View details for DOI 10.1016/j.ajo.2015.07.012
View details for PubMedID 26189086
EFFECT OF INTRAVITREAL TRIAMCINOLONE ACETONIDE ON HEALING OF RETINAL PHOTOCOAGULATION LESIONS
RETINA-THE JOURNAL OF RETINAL AND VITREOUS DISEASES
2013; 33 (1): 63-70
CNS neurons change their connectivity to accommodate a changing environment, form memories, or respond to injury. Plasticity in the adult mammalian retina after injury or disease was thought to be limited to restructuring resulting in abnormal retinal anatomy and function. Here we report that neurons in the mammalian retina change their connectivity and restore normal retinal anatomy and function after injury. Patches of photoreceptors in the rabbit retina were destroyed by selective laser photocoagulation, leaving retinal inner neurons (bipolar, amacrine, horizontal, ganglion cells) intact. Photoreceptors located outside of the damaged zone migrated to make new functional connections with deafferented bipolar cells located inside the lesion. The new connections restored ON and OFF responses in deafferented ganglion cells. This finding extends the previously perceived limits of restorative plasticity in the adult retina and allows for new approaches to retinal laser therapy free of current detrimental side effects such as scotomata and scarring.
View details for DOI 10.1523/JNEUROSCI.1044-12.2013
View details for Web of Science ID 000317723000012
View details for PubMedID 23595739
Macular infarction following intravitreal bevacizumab for treatment of central retinal vein occlusion.
Ophthalmic surgery, lasers & imaging : the official journal of the International Society for Imaging in the Eye
2012; 43: e73-9
To evaluate the effect of intravitreal triamcinolone acetonide (TA) on healing of retinal photocoagulation lesions using drug and laser dosing typically employed in clinical practice.Laser burns with a 267-μm retinal beam size at 532-nm wavelength were applied to 40 eyes of Dutch belted rabbits. Barely visible to intense lesions were produced with pulses of 5, 10, 20, and 50 milliseconds and power of 175 mW. Eyes received intravitreal injections of either 2 mg TA/50 μL or balanced salt solution administered either 1 week before or immediately after laser treatment. Lesion grades were assessed acutely ophthalmoscopically and by a masked observer histologically at 1, 3, 7, 30, and 60 days.Both TA groups demonstrated significant reduction in retinal thickness throughout follow-up compared with balanced salt solution groups (P < 0.001). The width of the lesions at 1 day after injection was not significantly different between groups. However, by 7 days, the lesions in balanced salt solution groups contracted much more than in the TA groups, especially the more intense burns, and this difference persisted to 2 months. The healing rate of the barely visible burns was not significantly affected by TA compared with the balanced salt solution control eyes.Triamcinolone acetonide injection previously or concurrently with photocoagulation significantly decreases laser-induced edema but interferes with lesions healing, thereby leaving wider residual scarring, especially persistent in more intense burns.
View details for DOI 10.1097/IAE.0b013e318261e34b
View details for Web of Science ID 000313422500008
Non-damaging Retinal Phototherapy: Dynamic Range of Heat Shock Protein Expression
INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
2011; 52 (3): 1780-1787
Bevacizumab, a monoclonal antibody against vascular endothelial growth factor (VEGF), is widely used for the treatment of macular edema associated with central retinal vein occlusion (CRVO). The authors present a series of three patients with CRVO who suffered apparent macular infarction within weeks of intravitreal administration of bevacizumab. Of the nearly 200 patients undergoing intravitreal injections of bevacizumab for this indication over a surveillance period of 3 years, this event occurred in three patients. This has not been described in the natural history of the disease and is associated with poor visual outcomes.
View details for DOI 10.3928/15428877-20120712-05
View details for PubMedID 22823029
SELECTIVE RETINAL THERAPY WITH MICROSECOND EXPOSURES USING A CONTINUOUS LINE SCANNING LASER
RETINA-THE JOURNAL OF RETINAL AND VITREOUS DISEASES
2011; 31 (2): 380-388
Subthreshold retinal phototherapy demonstrated clinical efficacy for the treatment of diabetic macular edema without visible signs of retinal damage. To assess the range of cellular responses to sublethal hyperthermia, expression of the gene encoding a 70 kDa heat shock protein (HSP70) was evaluated after laser irradiation using a transgenic reporter mouse.One hundred millisecond, 532 nm laser exposures with 400 ?m beam diameter were applied to the retina surrounding the optic nerve in 32 mice. Transcription from the HSP70 promoter was assessed relative to the control eye using a bioluminescence assay at 7 hours after laser application. The retinal pigmented epithelium (RPE) viability threshold was determined with a fluorescence assay. A computational model was developed to estimate temperature and the extent of cell damage.A significant increase in HSP70 transcription was found at exposures over 20 mW, half the threshold power for RPE cell death. Computational modeling estimated peak temperature T = 49°C at HSP70 expression threshold. At RPE viability threshold, T = 57°C. Similar temperatures and damage indices were calculated for clinical subvisible retinal treatment parameters.Beneficial effects of laser therapy have been previously shown to extend beyond those resulting from destruction of tissue. One hundred millisecond laser exposures at approximately half the threshold power of RPE damage induced transcription of HSP70, an indication of cellular response to sublethal thermal stress. A computational model of retinal hyperthermia can guide further optimization of laser parameters for nondamaging phototherapy.
View details for DOI 10.1167/iovs.10-5917
View details for Web of Science ID 000288965300070
View details for PubMedID 21087969
Improving the therapeutic window of retinal photocoagulation by spatial and temporal modulation of the laser beam
JOURNAL OF BIOMEDICAL OPTICS
2011; 16 (2)
To evaluate the safety, selectivity, and healing of retinal lesions created using a continuous line scanning laser.A 532-nm Nd:YAG laser (PASCAL) with retinal beam diameters of 40 ?m and 66 ?m was applied to 60 eyes of 30 Dutch-belted rabbits. Retinal exposure duration varied from 15 ?s to 60 ?s. Lesions were acutely assessed by ophthalmoscopy and fluorescein angiography. Retinal pigment epithelial (RPE) flatmounts were evaluated with live-dead fluorescent assay. Histological analysis was performed at 7 time points from 1 hour to 2 months.The ratios of the threshold of rupture and of ophthalmoscopic visibility to fluorescein angiography visibility (measures of safety and selectivity) increased with decreasing duration and beam diameter. Fluorescein angiography and live-dead fluorescent assay yielded similar thresholds of RPE damage. Above the ophthalmoscopic visibility threshold, histology showed focal RPE damage and photoreceptor loss at 1 day, without inner retinal effects. By 1 week, photoreceptor and RPE continuity was restored. By 1 month, photoreceptors appeared normal.: Retinal therapy with a fast scanning continuous laser achieves selective targeting of the RPE and, at higher power, of the photoreceptors without permanent scarring or inner retinal damage. Continuous scanning laser can treat large retinal areas within standard eye fixation time.
View details for DOI 10.1097/IAE.0b013e3181e76da6
View details for Web of Science ID 000286586500024
View details for PubMedID 20930656
Critical appraisal of the clinical utility of the dexamethasone intravitreal implant (Ozurdex) for the treatment of macular edema related to branch retinal vein occlusion or central retinal vein occlusion.
Clinical ophthalmology (Auckland, N.Z.)
2011; 5: 1043-1049
Decreasing the pulse duration helps confine damage, shorten treatment time, and minimize pain during retinal photocoagulation. However, the safe therapeutic window (TW), the ratio of threshold powers for thermomechanical rupture of Bruch's membrane and mild coagulation, also decreases with shorter exposures. Two potential approaches toward increasing TW are investigated: (a) decreasing the central irradiance of the laser beam and (b) temporally modulating the pulse. An annular beam with adjustable central irradiance was created by coupling a 532-nm laser into a 200-?m core multimode optical fiber at a 4-7 deg angle to normal incidence. Pulse shapes were optimized using a computational model, and a waveform generator was used to drive a PASCAL photocoagulator (532 nm), producing modulated laser pulses. Acute thresholds for mild coagulation and rupture were measured in Dutch-Belted rabbit in vivo with an annular beam (154-163 ?m retinal diameter) and modulated pulse (132 ?m, uniform irradiance "flat-top" beam) with 2-50 ms pulse durations. Thresholds with conventional constant-power pulse and a flat-top beam were also determined. Both annular beam and modulated pulse provided a 28% increase in TW at 10-ms duration, affording the same TW as 20-ms pulses with conventional parameters.
View details for DOI 10.1117/1.3542045
View details for Web of Science ID 000288939200056
View details for PubMedID 21361711
Adult Orbital Langerhans Cell Histiocytosis With Frontal Bone Involvement
OPHTHALMIC PLASTIC AND RECONSTRUCTIVE SURGERY
2009; 25 (2): 157-158
Macular edema is a common cause of visual loss in patients with retinal vein occlusions. Ozurdex(®), a dexamethasone intravitreal implant, has been shown in randomized controlled trials to reduce macular edema and improve visual acuity in patients with either branch retinal vein occlusions or central retinal vein occlusions. It was approved in the United States in 2009. Since then, new therapeutic agents and clinical data have emerged. The purpose of this review is to critically evaluate the clinical utility of Ozurdex(®) in the current treatment strategy of macular edema related to retinal vein occlusion.
View details for DOI 10.2147/OPTH.S13775
View details for PubMedID 21845032
Recent trends in the management of rhegmatogenous retinal detachment
SURVEY OF OPHTHALMOLOGY
2008; 53 (1): 50-67
A 28-year-old woman presented with a 2-week history of right upper eyelid swelling and intermittent frontal headaches. CT demonstrated an ill-defined superior right orbital mass with adjacent right frontal bone erosion and undeveloped frontal sinuses. The orbital biopsy revealed tissue strongly positive for CD1a and S100, diagnostic of Langerhans cell histiocytosis. The systemic workup was negative for multifocal lesions and for diabetes insipidus. In addition to subtotal resection, the patient was treated with a 6-month course of oral prednisone and intravenous vinblastine.
View details for DOI 10.1097/IOP.0b013e31819ac2d9
View details for Web of Science ID 000264585400028
View details for PubMedID 19300172
A novel mutation in intron 11 of the COL2A1 gene in a patient with Type 1 Stickler syndrome
RETINA-THE JOURNAL OF RETINAL AND VITREOUS DISEASES
2006; 26 (1): 106-109
It has been nearly a century since Jules Gonin performed the first intervention for rhegmatogenous retinal detachment, trans-scleral cautery, achieving successful outcomes in close to 50% of his cases. With the introduction of alternative surgical approaches in the last half-century, including Charles Schepens' scleral buckle technique and Robert Machemer's pars plana vitrectomy, the surgical success rates have risen to close to 90%. Nonetheless, despite dramatic progress in the success of reattachment surgeries, reasonable disagreement exists as to which approach (or combination of approaches) is the best form of surgical intervention for patients with rhegmatogenous retinal detachments. In this review, the authors summarize the current knowledge of retinal detachment, and examine emerging results from the first large scale, prospective, randomized, controlled clinical trials addressing the efficacy of these surgical approaches for retinal detachment, with the hope of identifying the most appropriate (evidence-based) therapeutic intervention for the treatment of rhegmatogenous retinal detachment.
View details for DOI 10.1016/j.survophthal.2007.10.007
View details for Web of Science ID 000252538400005
View details for PubMedID 18191657