BACKGROUND:
Degenerative diseases of the visual system classified as rare and, in particular, those
affecting the retina (known as Inherited retinal dystrophies, IRDs) cause very severe
functional deficits. Their onset is in many cases particularly early with a consequent
visual impact of extreme severity. They constitute a heterogeneous group from a clinical
point of view, but in all of them the loss of photoreceptors causes progressive vision
loss that can result in complete blindness.
These pathologies can be complicated by the presence of cataracts, epiretinal membrane
and macular oedema (10-50%), resulting in a worsening of visual acuity. While surgical
treatment is applicable for the first two complications, the treatment of macular oedema
can make use of several options. Oral or topical diuretics (Acetazolamide) are still the
first therapeutic approach and, if oedema persists despite treatment, intravitreal
corticosteroid injection has been used in various reports. The injection of anti-Vascular
Endothelial Growth Factor (VEGF) drugs and vitrectomy have also been proposed but with
conflicting results. The use of topical non-steroidal drugs has been studied and proven
to be valuable, although inferior to diuretic treatment in terms of visual recovery. The
use of intravitreal corticosteroids is also not without possible further complications
such as ocular hypertension and early onset of cataracts.
Despite some improvement in retinal oedema by taking the above-mentioned diuretics,
relapses can be observed at the end of therapy, reason for taking longer periods (>12
weeks) of therapy. However, the same chronic continuation of diuretic therapy is not
always desirable considering its possible adverse events such as tingling sensation,
malaise, altered taste sensation and gastrointestinal disorders.
RATIONALE:
The application of the micropulsed subthreshold retinal laser to reduce retinal oedema in
various diseases (diabetic oedema, central serous chorioretinopathy, age-related macular
degeneration and retinal vein occlusion) has recently gained wide acceptance.
Retinal threshold refers to the tendency of the laser to cause tissue bleaching resulting
in retinal cell death, the term sub-threshold implies that the laser uses such a small
amount of energy that it does not cause irreversible damage to retinal structures. The
term 'micropulsed' derives from the fact that the laser does not use a continuous wave
but has a sub-100% duty cycle and the use of 'off' times is what distinguishes this type
of laser from conventional lasers and allows the tissue to cool down, preventing
laser-induced retinal damage.
The main characteristics of this type of laser are therefore that it does not cause
visible retinal damage and that it has therapeutic effects.
One theory of how this type of laser works is through the action of the molecular
protective mechanisms of the Heat Shock Protein (Hsp) family in the retina, including
protein chaperone activity, stabilisation of the cytoskeleton and prevention of apoptosis
mainly through inhibition of cytochrome C release through the phenomenon of 'resetting'.
Another theory hypothesized the activation of leucocyte recruitment or remodeling of the
extracellular matrix in the choroid and retina. Possible mechanisms of increased trophic
factors (CNTF and FGF-2)14 and up-regulation of other factors (MMP-2, MMP-3, TNFα and
Nos2) are covered.
TRIAL DESIGN:
Prospective, interventional, single-centre, open-label study involving consecutive
enrolment (see sample size in section "Statistics") of patients with macular oedema in
retinal dystrophies.
Each patient referred to the Outpatient Clinical and Research Center of
Neuro-ophthalmology and Genetic and Rare Diseases with IRD and macular oedema treated for
3 months with diuretics and draining food supplements and without improvement of macular
oedema or increase of the same (reduction of post-therapy CRT ≤20% compared to
pre-therapy CRT) will be duly informed about the therapeutic option of this study
protocol. After verification of the criteria for inclusion in the study and after signing
of the informed consent, the patient will be considered eligible for treatment with
micropulsed laser by the physicians of the Clinical and Research Center of
Neuro-ophthalmology and Genetic and Rare Diseases and Medical Retina. The patient
enrolled in the study will be clinically analysed with the instrumentation indicated
below at regular intervals (screening/baseline, follow-up 1 [FU1] (1 month), FU2 (3
months), FU3 (6 months), FU4 (9 months), FU5 (12 months), FU6 (18 months) and FU7 (24
months).
