CSC is characterized by idiopathic serous detachment of the neurosensory retina. There are three theories on CSC pathogenesis:1, 2, 3, 4, 5
- Disorder of the outer BRB, which leads to choroidal vascular hyperpermeability.22
- Dysfunction of the RPE with a reversal of liquid transport.
- Damage of RPE due to shedding of outer photoreceptor segments with a primary intact BRB.
Clinical improvement in VA can only be achieved with resolution of subretinal fluid. The state of the RPE is crucial in the pathophysiology and prognosis of the disease itself, and should be taken into consideration for active treatment.
Standard focal thermal laser treatment, the oldest and still questionable therapeutic option, might be effective for the coagulation of the ALS on FA.23
However, because of iatrogenic thermal damage to the neurosensory retina and the RPE, it may only be considered in extrafoveal sites to minimize the risk of laser-induced absolute scotomata, contrast sensitivity loss, accidental foveal damage, retinal distortion, rupture of Bruch's membrane, and choroidal neovascularization.24
Recently, PDT has been used when the RPE lesion is juxta-foveal or subfoveal. Pharmacologically, PDT counteracts the choroidal hyperperfusion that is one pathophysiological cornerstone of CSC development due to local choroidal thrombosis. According to Yannuzzi et al
PDT treatment addresses directly the origin of subretinal fluid development. However, the optimal PDT technique, in terms of dosage, laser activation time, fluence, ICGA-guidance, and so on, is still undetermined.25, 26, 27
Furthermore, PDT can result in choroidal ischemia, RPE damage, or PDT-induced scotoma.28, 29
Rather than addressing choroidal hyperperfusion, nonthermal and non-damaging SDM photocoagulation allows for the application of laser energy to subfoveal and extrafoveal lesion sites and, by stimulating (or ‘tickling') a biological response in compromised RPE cells, it may induce the resolution of subretinal fluid by improving RPE cells' tight junctions and pumping functions mediated by upregulation of metalloproteinase enzymes.11, 12, 13
The 10-month results of our study cannot provide the long-term effects of SDM photocoagulation therapy in CSC, but they do indicate superior subretinal fluid resolution at month 6 and month 10, compared with observation or with intravitreal injections of BCZ. Interestingly, at week 6, the resolution of subretinal fluid was more pronounced in the BCZ group than in the SDM group (). This reversed later, with the SDM group showing superior fluid resorption at the 6-month and 10-month follow-up visits, possibly indicating an enhanced pumping function resulting from the biological resetting of pathologic RPE cells that could not occur at week 6 after SDM. On the other hand, BCZ injections on a monthly basis with enhanced dosage may be more effective than in the protocol that we used in this study, taking into consideration the associated clinical and economic risks of frequent intravitreal injections.17
Because all patients were treated and retreated with the same criteria (stronger leakage on FA with presence of more subretinal fluid than baseline), there was no bias to undertreat one group. The two patients with persistent leakage in the SDM group had two leakage sites and were male non-smokers. However, the nonresponders in the BCZ group had no common features in type of leakage, gender, or smoking habits. The decrease in subretinal fluid was most pronounced in the SDM group, but, because the retreatment criterion was active leakage on FA, some degree of subretinal fluid was observed in all groups at month 10. It is not clear whether additional SDM photocoagulation could have further decreased the subretinal fluid in these cases. This evaluation was not the goal of this study, but ongoing studies are in progress to examine this clinical setting.
No tissue reactions, that is, tissue heating, were observed during and at any point after the SDM photocoagulation treatment (), but long-term complications are not impossible and cannot be ruled out. To monitor the effects of photoreceptor/RPE dysfunction, we performed 10° perimetry, a rather indirect and subjective functional parameter. One limitation of our study is that 10° perimetry was performed without fixation control; therefore, we could not detect the possibility of scotoma development after the SDM photocoagulation treatment.
However, the BCZ group and the control groups indicated slight scotoma enhancement. Other studies have shown that intravitreal anti-VEGF agents effectively resorb subretinal fluid in up to 80% of the cases,14
whereas our study showed resolution only in 40% of the cases after 10 months. Our study seems to be the most thorough study on the intravitreal injection of BCZ treatment in CSC to date. Compared with SDM photocoagulation, intravitreal BCZ seems to reduce subretinal fluid faster, but requires frequent reinjections, regardless of the dosage. We used 1.25
mg of BCZ as described by Inoue et al
whereas some groups used 2.5
In our study, unlike in exudative AMD, intravitreal anti-VEGF injections were not associated with long-term damage to the RPE, the choriocapillaris, or the ganglion cells. However, CSC patients are usually younger, and ongoing intravitreal injections might not be a sustainable therapy. In addition, we should point out that this is a non-randomized study and there can be factors that may have potentially influenced the patients' choice between the treatment groups. It may be of interest that, on the basis of the data and information available at the time, which was clearly explained in our standardized informed consent process, 50% (26/52) of the patients elected to be assigned to the observation control group, which is still the current standard of care, 31% (16/52) opted for a minimally invasive intervention signing in the SDM photocoagulation group, and 19% (10/52) preferred the pharmacological intervention with intravitreal injections of BCZ. Thus, it was not a randomized trial but rather a real-life distribution with the bias that a patient, who opted for the SDM intervention is different by own decision and a biased selection over a patient with BCZ or no therapy. More studies should be conducted in the future, and our group is currently examining by randomization SDM with PDT in CSC in an ongoing trial.
Conversely, because of the absence of laser-induced retinal damage discernable at any time postoperatively, SDM photocoagulation, with no focal burn end point (or its consequences), represents an elegant medical approach and a true clinical alternative.
In conclusion, in this 10-month prospective, controlled study, SDM photocoagulation resulted superior to the intravitreal injections of 1.25
mg BCZ for resolution of subretinal fluid secondary to CSC. BCVA, macular perimetry, and metamorphopsia were improved after SDM photocoagulation, whereas the observed control group showed no improvements. The use of anti-VEGF injections as a monotherapy, or as adjunctive therapy, should be investigated in the future.