Subfoveal choroidal neovascularisation (CNV) is a major cause of severe visual loss in eyes with age related macular degeneration and high myopia or secondary to diseases affecting the Bruch's membrane and the layer of retinal pigment epithelium (RPE). Loss of vision results from ingrowth of new vessels from the choriocapillaries that are accompanied by fibrous tissue.1234 Macular photocoagulation study (MPS) has demonstrated that argon or krypton laser photocoagulation is useful in choroidal neovascular membrane (CNVM). Successful photocoagulation of a CNVM with the argon green or krypton red laser relies largely on the production of heat in the RPE, which is transferred to the surrounding tissue. This usually results in damage to the adjacent neurosensory retina.56 Hence its usage is limited to extrafoveal CNV.
The current view is that photodynamic therapy (PDT) with verteporfin is beneficial in subfoveal CNV secondary to AMD, pathologic myopia and ocular histoplasmosis. But it is expensive and needs several sessions of treatment.
Indocyanine green (ICG) absorbs and emits light in the near infrared range and is 98% bound to plasma proteins. The peak emission wavelength of the diode laser is 805 nm, and this coincides with the absorption spectrum of ICG. Hence, the photodynamic property of ICG dye can be used theoretically with infrared diode laser to obliterate the CNV at energy much less than that required to obliterate it with green or krypton red laser. There is a theoretical possibility that heat generated will be much less and cause minimal damage to the surrounding tissue. Animal experiments and human studies have demonstrated78910 three basic advantages of diode laser photocoagulation. First, infrared diode laser energy transmits readily through turbid retina as well as through retinal and subretinal haemorrhage. Second, the infrared diode laser induces occlusion of relatively deep choroidal vessels, including CNV feeder vessels, located underneath the CNV. Finally, the ICG acts as a new chromophore over the less pigmented proliferative RPE cells that cover many advanced cases of CNV, and thus helps improve the light absorption. Hence, using the photodynamic property of ICG dye, diode laser photocoagulation appears to be a viable option to treat juxtafoveal CNV.
This article presents the initial results of ICG enhanced diode laser photocoagulation for eyes with juxtafoveal CNV.
Materials and Methods
This was a pilot study of patients with primarily juxtafoveal CNV treated between 2001 and 2002. Patients of over 45 years of age with juxtafoveal CNV without any evidence of other macular disease were included in the study.
CNV in the study was defined as CNV located 200 micron or farther from the foveolar avascular zone (FAZ) center with blood or blocked fluorescence or both extending within 200 micron from the FAZ. Patients with a history of laser photocoagulation with subfoveal scar in the fellow eye were excluded from the study. Visual acuity was not the criterion for exclusion.
All patients underwent the Snellen's visual acuity test, slit lamp examination, Amsler grid, and fundus examination with 90 Doptre lens and indirect ophthalmoscopy. During the initial visit, after the ophthalmic examination, fundus photography, fundus fluorescein angiography and ICG angiography were performed. On all follow-up visits, ICG angiography was done on all the patients. The pattern of the follow-up visits was every month for the first three months and the 6th, 9th and 12th months thereafter. However, a minimum follow-up of six months was desired so as to permit useful comparison with those following conventional laser treatment.11
Prior informed consent was taken and subjects were informed about the treatment and follow-up protocol. Required information was substantiated whenever patients desired any additional information.
Oculight SLx trimode (Iris Medical) 810 nm diode laser was used. After dilatation of the pupil, the macula was re-examined and compared with the angiogram to confirm the area of treatment. A quadraspheric fundus contact lens (VOLK Optical Inc., Mentor) was used to focus on the treatment area. Laser parameters were fixed and 25 mgm (in 5 ml) of intravenous injection of ICG dye was injected into the peripheral arm vein followed by 5 ml of saline flush. Two to three minutes later, laser was applied. This is important as the concentration of dye in the choroidal vasculature is sufficiently high12 at this time of laser application. The treatment given was on the basis of preoperative fluorescein and ICG angiography images. Confluent burns were applied to the entire extent of the CNVM. Mild gray colour change or minimal visible change was taken as the endpoint of treatment. Care was taken to ensure that the laser spot did not extend beyond the area of CNVM. Immediately after the application of laser, the area of treatment was evaluated using ICG mode of confocal scanning laser ophthalmoscope (Heidelberg Retinal Angiograph, Heidelberg Engineer Inc., Heidelberg, Germany). Improvement of vision was defined as one line gain, stabilisation as one line loss and worsening as more than one line loss.
The age of the eleven patients ranged from 45 to 80 years. Five (45.4%) patients were males. All patients had completed at least 12 months of follow-up. Eight eyes (72.7%) had AMD, two eyes had myopia and one eye had angioid streak. Left eye was involved in 72.7% (8/11 eyes). Angiographically the CNV was predominantly classic in 36.4% (4/11) and occult in 63.6% (7/11).
None of the patients complained of pain during or after the treatment. All patients received direct confluent treatment to the specified area. Immediate evaluation of the treated lesion with ICG mode of confocal scanning laser ophthalmoscope suggested occlusion of the membrane. No visible change to minimal graying was seen clinically (Figure 1). The average time of initiation of treatment from the time of injection of ICG dye was 3 minutes+23.4 seconds. The power ranged from 300 mW to 630 mW (mean: 397.2+106.6 mW), spot size of 300 to 500 microns (mean: 463.63+80.9 microns) and number of laser spots varied from 13 to 444 (mean: 187.18+124.8) (Table 1). In 10 eyes, the number of laser spots ranged from 13 to 301 (mean: 161.5+96.14) and one eye needed 444 spots due to large lesion size. Repeat treatment was not performed in any of the patients.
The initial visual acuity was>6/12 in 3 eyes (27.2%), 6/18 - 6/36 in one eye (9%)and< 6/60 in 7 eyes (63.64%). Poor vision was due to associated damage in the fovea either due to myopic chorioretinal atrophic changes or either extensive drusenoid and RPE alteration, scar or geographic atrophy involving the fovea. All patients were advised PDT, but they refused mostly because of the high costs it entailed.
The final visual acuity at the end of at least 12 months follow-up was nearly similar to the presenting vision. The final vision was>6/12 in one eye, 6/18 - 6/36 in 3 eyes and< 6/60 in 7 eyes. The change from the presenting vision is shown in table 2.
Two eyes (18.2%) with initial vision of 6/12 or better had recurrence between 6 and 9 months. Two eyes from the visual acuity group of 6/60 or worse showed deterioration due to extension of the scar. Subretinal haemorrhage on the outer aspect of the CNV was seen in one patient on the first follow-up visit without any extension of the membrane. The haemorrhage resolved at the end of the third month.
One of the two patients with recurrence refused retreatment and consented for PDT. In the other patient the CNV healed by the ninth month (Figure 2) .This patient had CNV secondary to angioid streak. Thus, 9 of 11 (81.8%) patients had successful anatomical occlusion of the membrane. (Figure 3)
One patient had one disc area of choriocapillaries non - perfusion (occlusion) due to inadvertent extended area of treatment (Figure 4).
Eleven patients with juxtafoveal CNV, both classic and occult who received ICG dye enhanced diode laser photocoagulation were evaluated. Since the MPS study indicates that laser photocoagulation may be beneficial in successful closure of juxtafoveal CNV4 with a high possibility of damage to the neighbouring visual apparatus,56 it appears justified to reduce the thermal injury to minimum by confining the treatment to the ICG dye containing CNV complex only. This treatment method has been tried earlier in poorly defined subfoveal CNV and subfoveal CNV associated with AMD.1012 This is the first pilot study to report ICG dye enhanced diode laser photocoagulation for juxtafoveal CNV (MEDLINE).
In this study, the CNV occlusion rate was 100% at least upto 6 months and reduced to 81.8% due to recurrence in 2 patients. It also shows that the treatment should be confined to the specific CNV demarcated area lest there should occur occlusion of the surrounding choriocapillaries (Figure 4).
In this study, 7 (63.6%) of 11 eyes showed either stable or improved visual acuity by at least one line at 12 months. Earlier studies have also shown 68-90% stabilisation of vision.1012 Both these studies and the present study have shown anatomical occlusion of the CNV complex and comparable visual status changes. But VA changes cannot be compared due to different anatomical location of CNV.
Recurrence rate was almost comparable to the study of Obana et al10 and lower than Reichel et al12 study or the MPS study. A recurrence rate of 43% is typically seen after argon laser photocoagulation within one year.13 The present study and Obana et al10 show low recurrence rate. The low rate of recurrence could be due to use of less thermal energy and less collateral damage to the surrounding choriocapillaries and neurosensory retina.
The present study was retrospective and no controls were used. In conclusion, this preliminary pilot series has been able to show some potential benefits and limitations. A larger prospective controlled randomised clinical trial can further define the role of ICG enhanced diode laser photocoagulation in the treatment of juxtafoveal choroidal neovasular membrane.
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