Purpose
To evaluate the effect of half-dose verteporfin photodynamic therapy (PDT) on macular function in cases of central serous chorioretinopathy (CSC).
Design
Interventional case series.
Methods
A total of 24 eyes from 24 cases of CSC were included in this study. In each eye, at baseline and 1, 3, and 6 months after half-dose PDT, logMAR best-corrected visual acuity (BCVA); central 10-degree, 20-degree, and paracentral 10-degree to 20-degree retinal sensitivity; and also mean retinal sensitivity results for each case over the area that was treated with half-dose PDT (PDT spot area) by MP-1 microperimetry and optical coherence tomography (OCT) foveal morphologic changes were assessed. The MP-1 microperimetry sensitivity map was overlaid onto an indocyanine green angiography image recorded on a Heidelberg scanning laser ophthalmoscope using dedicated MP-1 software to evaluate the PDT laser spot area.
Results
After treatment, BCVA and central 10-degree, 20-degree, paracentral 10-degree to 20-degree, and PDT laser spot area retinal sensitivity were improved significantly. In OCT in 20 of 24 eyes (83%), subretinal fluid (SRF) was resolved 1 month after half-dose PDT. At 3 and 6 months after treatment, SRF was resolved at all eyes. None of the patients in this study developed any systemic or ocular adverse events associated with verteporfin treatment.
Conclusion
Half-dose verteporfin PDT induced a significant increase in central 10-degree, 20-degree, paracentral 10-degree to 20-degree, and also PDT laser spot area retinal sensitivity over 6 months in cases of CSC.
Central serous chorioretinopathy (CSC), which is characterized by focal serous retinal detachment in the macular area, is often accompanied by pinpoint leakage from the retinal pigment epithelium (RPE) that is seen on fluorescein angiography. Best-corrected visual acuity (BCVA) is often only moderately decreased, and can be improved with the addition of a small hyperopic correction. In most cases, CSC is self-limited and resolves spontaneously over 4 to 6 months, albeit with mild color- or contrast-sensitivity alterations. In approximately 30% to 50% of cases, there may be recurrence, and patients may even experience visual loss with BCVA of 20/200 or worse because of chronic neurosensory retinal detachment and RPE atrophy. With the use of indocyanine green angiography, it has been demonstrated that CSC primarily affects the choroidal circulation and causes multifocal areas of choroidal vascular hyperpermeability.
There have been several reports that appear to show that photodynamic therapy (PDT) is an effective treatment for chronic CSC. In these studies BCVA is the standard way to measure visual performance, but it does not describe the full extent of the functional impact on visual performance in patients with compromised central visual fields attributable to chronic CSC. Evaluation of retinal sensitivity and central retinal field function using microperimetry, which is 1 of the functional evaluation techniques, is more informative than BCVA testing alone. The value of testing macular function by central microperimetry in chronic CSC has been shown extensively. MP-1 microperimetry allows automated functional analysis of the macula associated with real-time correction of eye movements. The procedure provides exact localization of the tested region on the retina, even in patients with unstable fixation. Microperimetry is also a valuable tool in evaluating the safety of new therapeutic strategies. Improved or stable retinal sensitivity and visual fields are important indicators of the absence of treatment-induced toxic effects.
In this study we evaluated changes in functional macular mapping obtained by the MP-1 microperimeter in patients with chronic CSC during a 6-month follow-up of half-dose PDT therapy.
Methods
All cases of symptomatic chronic CSC of 4 months or more in duration were recruited to the study. Inclusion criteria included BCVA of 20/200 or better, presence of subretinal fluid (SRF) on optical coherence tomography (OCT), and presence of abnormal dilated choroidal vasculature on indocyanine green angiography. Patients were excluded who had received previous PDT for chronic CSC or had evidence of choroidal neovascularization (CNV) on fluorescein angiography, corneal opacity, a history of ocular surgery, glaucoma or ocular hypertension, a history of intraocular inflammation such as anterior or posterior uveitis, multifocal choroiditis, a history of retinal detachment, a history of ocular trauma, a history of steroid usage and optic neuropathy, or refractive error more than ±6.00 diopters. All patients underwent a complete ophthalmic examination, including BCVA, indirect ophthalmoscopy, fluorescein and indocyanine green angiography, microperimetry, and OCT. BCVA in each eye was measured at 4 meters with Early Treatment of Diabetic Retinopathy Study (ETDRS) protocol with modified ETDRS distance chart transilluminated with a chart illuminator (Precision Vision, Bloomington, Illinois, USA). Vision results were quantified as logMAR units. Fluorescein and indocyanine green angiography were performed on a Heidelberg scanning laser ophthalmoscope (Heidelberg Engineering, Heidelberg, Germany). OCT scans were recorded on an OCT 3000 scanner (Carl Zeiss Ophthalmic System, Humphrey Division, Dublin, California, USA).
Macular sensitivity was evaluated by MP-1 microperimetry (Nidek, Vigonza, Italy). The MP-1 provides a 45-degree nonmydriatic view of the fundus with automated correction for eye movements. Goldmann III stimuli and a 4-2-1 staircase strategy were used, and a circular test grid with 74 stimulus locations covering an area of 20 degrees was applied. The microperimetry sensitivity map was also overlaid onto other images using dedicated MP-1 software. This software allows for the exact superimposition of sensitivity data to different images separately (infrared, autofluorescence, fluorescein and indocyanine green angiography). The superimposition is obtained by the semiautomatic detection of 2 identical anatomic landmarks on both images. This software has previously been tested for validity and repeatability. To assess microperimetry results over the area that was treated with PDT, we superimposed sensitivity data on the indocyanine green angiography image of the Heidelberg scanning laser ophthalmoscope.
The mean retinal sensitivities at the 28 locations (number of measurement points) covering the central 10-degree field, 76 locations covering the central 20-degree field, and 48 locations covering the paracentral 10-degree to 20-degree field, and number of measurement points and mean retinal sensitivity results for each patient over PDT area were determined. The stimuli were projected on a white background with background illumination set to 1.27 cd/m 2 and a stimulus presentation time of 200 ms. The fixation target was varied in size (2-degree or 4-degree red cross) according to the patient’s BCVA. All patients had to demonstrate good collaboration in the microperimetry test, which means a prompt and correct understanding of the technique and a good capacity for concentration. Each patient underwent a preliminary practice test prior to the definitive microperimetry test to standardize any learning effect.
PDT used half the normal dose of verteporfin (Visudyne, Novartis AG, Bülach, Switzerland); that is, 3 mg/m 2 infusion of verteporfin. Verteporfin was infused over 8 minutes, followed by laser 10 minutes from the commencement of infusion. A total light energy of 50 J/cm 2 for 83 seconds was delivered to the area of choroidal hyperperfusion as observed in indocyanine green angiography. In all cases this area was within the central 20 degrees. After treatment, protective spectacles were given, and patients were instructed to avoid strong light for 2 days. The patients had further microperimetry tests, as part of follow-up, 1, 3, and 6 months after treatment. The patient’s subjective feelings after treatment were sought at each follow-up examination.
The repeated ANOVA and Bonferroni post hoc test were used to assess improvement in function after treatment. Mann-Whitney U test was used to assess differences between groups. SPSS for Windows, version 15.0 (SPSS Inc, Chicago, Illinois, USA), was used for the statistical analysis. P < .05 was considered statistically significant.
Results
Twenty-four eyes from 24 cases of chronic CSC were included in this series. Patients were 21 men and 3 women, whose ages ranged from 34 to 55 years (mean, 46 years). Pretreatment BCVA range was 20/25 to 20/200. All eyes had had 1 or more previous CSC episodes, and the mean duration of the current episode was 4 to 6 months. Before treatment all patients had SRF on OCT examination. Before treatment 10 of 22 eyes (45%) had bilateral involvement on fluorescein angiography, with some RPE changes and window defects in the other eye. All patients had subjective improvement of symptoms. The PDT was applied within the central 20-degree area in all patients. The mean spot size was 2500 ± 455 μm (range 1700-3300 μm). The clinical characteristics of eyes with CSC at baseline and 1, 3, and 6 months after treatment are reported in Table 1 .
| Visual Acuity (logMAR) | Central 20-Degree Retinal Sensitivity (dB) by MP-1 Microperimetry | Photodynamic Therapy Laser Spot Size (μm) | ||||||||
|---|---|---|---|---|---|---|---|---|---|---|
| Patient | Age (Years) | Baseline | 1 Month | 3 Months | 6 Months | Baseline | 1 Month | 3 Months | 6 Months | |
| 1 | 49 | 0.4 | 0.1 | 0.1 | 0.1 | 10.3 | 13.1 | 14.4 | 14.5 | 2500 |
| 2 | 37 | 0.2 | 0.1 | 0 | 0 | 10.1 | 10.8 | 14.9 | 17.8 | 2900 |
| 3 | 45 | 1 | 0.7 | 0.7 | 0.5 | 9.5 | 11.9 | 11 | 11.2 | 3300 |
| 4 | 55 | 1 | 1 | 1 | 0.8 | 4.6 | 5 | 5.3 | 9.7 | 2000 |
| 5 | 44 | 0.3 | 0.3 | 0.3 | 0.3 | 6.5 | 11.6 | 10.3 | 10.8 | 1800 |
| 6 | 47 | 0.7 | 0.7 | 0.7 | 0.7 | 6.3 | 7.8 | 8.2 | 8 | 3200 |
| 7 | 42 | 0.5 | 0.5 | 0.3 | 0.3 | 12.7 | 13.9 | 14.1 | 14.3 | 2300 |
| 8 | 55 | 1 | 1 | 1 | 1 | 5.7 | 6.6 | 7 | 7.8 | 2400 |
| 9 | 45 | 0.7 | 0.5 | 0.5 | 0.3 | 5.4 | 10.1 | 9.9 | 13.3 | 3000 |
| 10 | 52 | 1 | 1 | 1 | 1 | 6.6 | 8.2 | 8.3 | 8.8 | 3300 |
| 11 | 44 | 0.3 | 0.3 | 0.2 | 0.2 | 14.7 | 15.7 | 15.6 | 16.2 | 2400 |
| 12 | 55 | 0.5 | 0.3 | 0.3 | 0.2 | 14 | 14.2 | 15.2 | 15.3 | 2100 |
| 13 | 55 | 0.3 | 0.1 | 0.1 | 0.2 | 12.3 | 13.3 | 13.6 | 14 | 2700 |
| 14 | 44 | 0.5 | 0.5 | 0.5 | 0.5 | 7.9 | 10.8 | 13.4 | 13.5 | 2500 |
| 15 | 45 | 0.1 | 0 | 0 | 0 | 13.6 | 14.3 | 15.2 | 15.3 | 1700 |
| 16 | 55 | 0.3 | 0.1 | 0 | 0 | 12.9 | 15.3 | 17.4 | 16.6 | 2600 |
| 17 | 45 | 0.1 | 0 | 0 | 0 | 12.8 | 14.2 | 16.7 | 16 | 2300 |
| 18 | 54 | 0.5 | 0.3 | 0.2 | 0.2 | 5.7 | 7 | 8.8 | 8.5 | 1900 |
| 19 | 53 | 0.3 | 0.2 | 0.1 | 0.2 | 16.1 | 16.7 | 16.5 | 16 | 2700 |
| 20 | 35 | 0.3 | 0.3 | 0.3 | 0.3 | 14.2 | 16.2 | 16.5 | 16.3 | 2300 |
| 21 | 42 | 0.3 | 0.2 | 0 | 0 | 12.2 | 15.8 | 15.6 | 15.7 | 2100 |
| 22 | 34 | 0.3 | 0 | 0 | 0 | 13 | 16.7 | 17.1 | 16.9 | 2700 |
| 23 | 50 | 0.3 | 0.2 | 0 | 0 | 13 | 15 | 15.4 | 15.5 | 2400 |
| 24 | 36 | 0.3 | 0 | 0 | 0 | 12.4 | 17 | 18.4 | 17.7 | 3000 |
| Mean ± SD | 46 ± 6 | 0.47 ± 0.28 | 0.35 ± 0.32 | 0.30 ± 0.34 | 0.28 ± 0.31 | 10.52 ± 3.53 | 12.55 ± 3.56 | 13.28 ± 3.71 | 13.74 ± 3.21 | 2500 ± 455 |
| P a | <.001 | <.001 | <.001 | <.001 | <.001 | <.001 | ||||
a Compared with pretreatment by repeated analysis of variance and Bonferroni post hoc test.
Compared with pretreatment BCVA (log MAR) (0.47 ± 0.28), the mean post-treatment BCVA improved significantly (0.35 ± 0.32 at 1 month [ P < .001], 0.30 ± 0.34 at 3 months [ P < .001], and 0.28 ± 0.31 at 6 months [ P < .001]). As measured with microperimetry, mean retinal sensitivities within the central 10-degree, 20-degree, and paracentral 10-degree to 20-degree fields, which were 8.17 ± 4.31, 10.52 ± 3.53, and 11.79 ± 3.33 dB at baseline, improved to 11.08 ± 4.61 ( P < .001), 12.55 ± 3.56 ( P < .001), and 13.51 ± 3.47 dB ( P < .001) at 1 month, and to 12.45 ± 4.32 ( P < .001), 13.28 ± 3.71 ( P < .001), and 13.74 ± 3.75 dB ( P < .001) at 3 months and to 12.95 ± 3.90 ( P < .001), 13.74 ± 3.21 ( P < .001), and 14.22 ± 3.41 dB ( P < .001) at 6 months.
The mean microperimetric numbers of measurement points in PDT area were 14.5 ± 3.6 (range 9 to 22 locations). Compared with pretreatment mean retinal sensitivity over the PDT area, 7.41 ± 4.29 dB, the post-treatment mean retinal sensitivity over the PDT area improved significantly (10.39 ± 4.45 dB at 1 month [ P < .001], 11.72 ± 4.53 dB at 3 months [ P < .001], and 12.23 ± 4.07 dB at 6 months [ P < .001]) ( Table 2 ).
