الفهرس 
IntroductionOnly 14 pages are availabe for public view
 |  | from | 95 |  |  |
| | | from | 95 | | |
Abstract
Hydroxychloroquine (HCQ), sold under the brand name Plaquenil (Sanofi-Aventis), is an antimalarial drug that has gained widespread use in treating various autoimmune diseases, including systemic lupus erythematosus and rheumatoid arthritis. Accordingly, in recent years there has been an increased emphasis on more effective screening measures utilizing multimodal imaging techniques to elicit early signs of toxicity before the characteristic advanced changes manifest clinically. In the earliest stages of HCQ toxicity, patients are often asymptomatic with preservation of visual acuity. However, perceptive individuals may report difficulty with night vision, glare or paracentralscotomas that interfere with reading.
The scotoma typically becomes apparent to the patient well before changes are seen on examination. While recognition of subtle foveal depigmentation has been described in some cases of early toxicity, this was only after corroboration with ancillary imaging studies.
On the other hand, visible bull’s-eye retinopathy, characterized by a ring of retinal pigment epithelium degeneration often sparing the foveal center, is a late finding indicative of advanced damage. Thus, ophthalmoscopy alone is not sufficient to screen for HCQ toxicity.
Retinal pigment epithelium(RPE|) is a monolayer of approximately hexagonal cells located between the neurosensory retina and the choroid. Its functions include rod’s outer segment (OS) phagocytosis. Each RPE cell supports approximately 45 photoreceptors and phagocytes approximately 3 billion OSs over a lifetime. The byproducts of this process are stored in lysosome residual bodies as lipofuscin. LFs are
ubiquitous lipoproteic pigments accumulating in postmitotic cells in nervous, myocardial and retinal cells during ageing. LF occupies approximately one-third of the RPE cells cytoplasm over the age of 70 and emits AF when excited by specific wavelengths. N-retynilidene-N-retynilethanolamine (A2E) represents the LF’s major fluorophore. It accumulates in the lysosomes because it is not recognized by lytic enzymes as a consequence of photo-oxidative alterations.
Its chemical structure is responsible for the detergent-like action on the RPE cells membranes, and its conjugated double bonds promote light absorption and fluorescence emission.
Fundus autofluorescence (FAF) is the concept of using naturally occurring fluorescence from the retina to provide an indicator of RPE health. Illuminating the retina with blue light at 488 nm causes certain cellular components (Lipofuscin (LF) & melanolipofuscin) to “glow” without injecting any dye. This glow (fluorescence) returning from the retina can be used to create a black-and-white image which can be interpreted by recognizing characteristic patterns, in much the same way.
In-vivo FAF was observed for the first time during vitreous fluorophotometry. Subsequently von Rückmann et al. introduced the confocal scanning laser ophthalmoscope (cSLO) that elicits retinal AF by scanning the retina with a low-powered laser beam. By adopting confocal optics, this technology overcomes the interference of autofluorescent preretinal structures, such as the lens.
Normal FAF appears slightly different with green-AF showing a less e Confocal optics ensure that the reflectance of the scanning laser and the retinal fluorescence are derived from the same optical plane. The exciting and emission filters of standard confocal ophthalmoscopes are 488 nm (blue light), and 500-520 nm respectively so that cSLO-AF is called also blue-AF or short-wavelength (SW)-AF. Near infra-red (NIR)-AF also uses confocal optics, but with longer exciting wavelength (790 nm). The emission is above 800 nm and its signal is 60-100 times weaker than what seen in blue light AF. Melanin is the main fluorophore in NIR-AF, so fluorescence is more intense in choroidal tissue and RPE cells due to higher melanin density.