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To present the 2‐year outcomes of surgical removal of non‐age‐related macular degeneration (AMD)‐related choroidal neovascular membranes and to evaluate any association between visual outcome and baseline clinical factors.
Retrospective consecutive case series. All patients who had surgery for non‐AMD‐related choroidal neovascularisation (CNV) between November 1997 and March 2003 under the care of a single surgeon (WA) were included in the study. Baseline data including patient age, duration of subfoveal CNV, preoperative visual acuity (VA), lesion size, lesion components and aetiology were collected. The primary outcome was VA change with secondary outcomes retinal detachment, operative peripheral retinal break formation, CNV recurrence and cataract.
A total of 52 eyes were included in the study. The aetiology of CNV was: punctate inner choridopathy 21 (40%); idiopathic 8 (15%); pathologic myopia 6 (12%); ocular histoplasmosis syndrome 1 (2%); and other 16 (31%). The mean age of patients was 41(range 14–72) years. 24‐month follow‐up was available for 41 (80%) eyes. The mean logMAR equivalent baseline acuity was 1.1 and mean lesion size 1.2 disc areas. An improvement in VA >1 Snellen line was noted in 26 (63%) eyes, whereas 10 (24%) eyes remained the same (within 1 line) and 5 (12%) lost >1 line of acuity. Improvement in VA was associated with worse baseline VA (84% for eyes with VA 6/36 vs 31% for those with VA>6/36, p=0.001). No evidence of association between 2‐year visual outcome and any other baseline factor under study was observed. Peripheral retinal breaks were noted in 5 (10%) eyes at the time of surgery, and 3 (5.8%) eyes developed postoperative retinal detachments. Persistent/recurrent CNV was noted in 17 (33%) eyes. The median time to presentation of CNV in these eyes was 27 (range 2–172) weeks. Five eyes underwent cataract surgery during the follow‐up period. The mean age of these patients was significantly higher than the mean age of those who did not require cataract surgery (57 vs 37 years, p=0.014).
Surgical excision of non‐AMD‐related CNV resulted in improvement of VA in the majority of eyes. Worse presenting acuity was associated with better visual improvements.
A retrospective consecutive case series of surgical removal of choroidal neovascular membranes (CNVM) related to non‐age‐related macular degeneration (AMD) from a single surgeon was studied. Two‐year results of surgery are presented, showing a 63% frequency of improved acuity. Postoperative persistence/recurrence of choroidal neovascularisation (CNV) was noted in 33% of eyes, and 6% developed postoperative retinal detachment. Improved acuity was associated with worse baseline vision.
Subfoveal choroidal neovascularisation is commonly seen in ocular histoplasmosis syndrome, punctate inner choroidopathy (PIC) and myopia, and can be idiopathic. Grossniklaus and Gass presented evidence to support a different histopathological morphology of these non‐AMD‐related membranes.1,2 Surgical excision has recently been shown to be an effective way of stabilising or improving acuity in many eyes with non‐AMD‐related CNV, but not in AMD.3,4 The retinal pigment epithelium lies superficial to the neovascular complex in AMD and is lost with surgical excision of these AMD‐related membranes, resulting in loss of the overlying photoreceptors and poor visual outcomes.1 The present study presents the outcomes of surgical intervention for non‐AMD‐related CNV performed by a single surgeon over a 5‐year period, with particular emphasis on the 2‐year results.
All eyes undergoing surgical removal of non‐AMD‐related CNVM under the care of a single surgeon between November 1997 and March 2003 were included in the study (these dates were chosen to prevent overlap with a previous series from the same institution,5 while allowing 2 years of follow‐up). The indication for surgery was type II CNV with symptomatic visual loss present for at least 2 months (to give time for spontaneous resolution). Patients older than 50 years were eligible, provided there were no intermediate or large drusen (63 μm) diagnostic criteria of AMD.6
The medical charts were reviewed retrospectively. Baseline data collected included patient age at the time of surgery, primary cause of CNVM and any previous treatment received for the CNVM (eg, systemic steroids, argon laser and PDT). Care was taken to document the date of onset of symptoms, the first date the neovascular lesion was documented to be subfoveal (if applicable) and the date of surgery. Preoperative angiograms were graded, and lesion site, size and components were assessed. The neovascular component of the lesion was classified as classic/occult in the standard way.7,8
Peroperative complications, particularly peripheral retinal breaks, were recorded. The surgical technique was similar to that described by Thomas and Kaplan.9 A standard pars plana vitrectomy is carried out with peeling of the posterior hyaloid. An angled 33‐gauge cannula (Synergetics, O'Fallon, Missouri, USA) is then passed through the retina into the subretinal space. The site of entry is chosen to be at least one disc diameter from the fovea, and close to the edge of the CNV membrane, approaching from either the superonasal or the superotemporal direction, depending on the configuration of the membrane and the retinal blood vessels. A small amount of balanced salt solution is then injected slowly into the subretinal space through the cannula, sufficient to create a small retinal detachment over the membrane. The tip of the cannula is then used to gently probe the membrane to divide any adhesions between it and the surrounding tissue. Subretinal horizontally opposed forceps (Synergetics) are then inserted through the same retinotomy, and the membrane grasped firmly, then slowly extracted, paying attention to avoid tearing the underlying retinal pigment epithelium, or allow bleeding from feeder vessels. As a precaution, the infusion bag is elevated to 90 cm just before membrane removal. Once the membrane is freed and pulled into the preretinal space, the instruments are kept in the eye, and the bag is left elevated for 1 min, before slowly lowering it while watching the feeder vessel for bleeding. If bleeding is noted, the bags are elevated again for another minute. A partial fluid/air exchange is then performed and the entry sites checked, before closing the sclerostomies with 7/0 vicryl. Postoperatively patients are asked to posture face down for 6 h to facilitate reattachment of the macula. Figure 11 shows the typical preoperative and postoperative appearances.
The primary outcome of interest was visual acuity (VA) change relative to baseline at 2 years. Improved VA was defined as more than one Snellen line improvement, same as within one line and worse as loss of more than one Snellen line. Mean visual acuities were calculated by converting Snellen acuity to a logMAR equivalent. Absent VA values were estimated if there was a valid value both preceding and succeeding the missing data point, and assuming a linear change in logMAR acuity with time. Secondary outcomes were CNV recurrence/persistence, peripheral retinal break, postoperative retinal detachment and cataract surgery.
Logistic and multiple variable linear regressions were used to assess evidence of any association between visual outcome at 24 months and each baseline factor. In the logistic regression model, visual outcome was analysed as dichotomous—improved vs same or worse. In the linear regression model, associations between final VA and baseline factors were assessed after adjusting for differences in baseline VA.
All analyses were conducted in Stata V.8.2 for Windows.
A total of 52 eyes of 50 patients underwent surgical excision of non‐AMD‐related CNVM during the study period. The mean age of patients at the time of surgery was 40 (range 14–72; SD 13.4) years. In all, 31 patients were female and 19 male. Table 11 summarises the aetiology of CNV. Sixteen eyes had received prior treatment with systemic steroids alone (9 eyes with PIC, 2 myopic and 5 with other diagnoses), 2 with argon laser alone (one PIC and one pseudoxanthoma elasticum) and 2 with argon laser and systemic steroids (one PIC and one periodical occupational health survey (POHS)). Treatment response in all cases was thought to be insufficient to obviate the need for surgery. None had received prior treatment with photodynamic therapy. Preoperative fluorescein angiograms were available in 48 of 52 (92%) eyes. Of these, 44 of 48 lesions were subfoveal, and 4 of 48 were judged not to be subfoveal at the preoperative angiogram. The median lesion size was 1.2 disc areas (range 0.2–2.9, SD 0.77). Angiographically the CNV component was graded as classic, with no occult component in 45 of 48 (94%) angiograms, predominantly classic in 2 (4%) and occult with no classic in 1 (2%). In 2 of 48 eyes, haemorrhage was judged to occupy >50% of the total lesion area. In no eyes was a pigment epithelial detachment noted.
One patient has been excluded from the presentation of acuity data. She was a 25‐year‐old woman who reported an acuity of hand motions vision in the operative eye (and count fingers in the otherwise normal fellow eye) 4 years postoperatively, despite a good macular appearance with no sign of CNV recurrence. No other follow‐up visits were attended either before this or subsequently. Electrophysiological testing was performed, which showed a normal pattern electroretinogram and full‐field electroretinogram in both eyes, a normal pattern reversal visual evoked potential in the non‐study eye, and a pattern reversal visual evoked potential with a major positivity at 110 ms of amplitude 8 μV (mildly reduced and delayed) in the study eye. This was consistent neither with her low reported acuity nor with acute zonal occult outer retinopathy, and non‐organic visual loss was suspected.
Table 22 presents the VA outcomes. One‐year follow‐up was available for 47 of 51 (92%) eyes, and two‐year follow‐up for 41 of 51 (80%) eyes. The main reason for loss to follow‐up was patients being discharged back to their regional ophthalmology department and subsequently not attending the requested review appointments. At the 24‐month visit, 26 of 41 (63%) eyes had improvement of more than 1 Snellen acuity line, 10 of 41 (24%) eyes were the same and 5 of 41 (12%) worse. None of these 41 eyes deteriorated between the 12‐ and 24‐month review appointments, and four eyes gained Snellen acuity and moved from the “same” group to the “improved” group. Both of the two eyes with haemorrhage >50% of the total lesion area had improved acuity at 2 years.
The frequency of recurrent CNV using all available follow‐up (not just 2‐year data) was 16 of 52 (31%), and of persistent CNV 1 of 52 (2%). The timing of recurrence could be estimated in 15 of these eyes, and the median time to recurrence was 27 weeks (range 48 days–40 months). One eye first developed a recurrence >4 years postoperatively, having been definitely recurrence free at the 48‐month visit. All other recurrences presented within the first two postoperative years. Improvement in VA at 2 years was noted in 9 of 14 (64%) eyes with persistence or recurrence, and in 18 of 27 (67%) eyes without recurrence. Subsequent management of CNV was repeat surgery in 4 eyes, systemic steroids in 1 eye and no treatment in 12 eyes. Among eyes undergoing repeat membranectomy surgery, two had improved acuity at 24 months, one the same at 24 months, and one improved acuity at 12 months with no further follow‐up (all acuities relative to baseline).
Peroperative retinal breaks were noted in 5 of 52 (10%) eyes. One patient required lensectomy at the time of CNV removal due to operative posterior lens capsule trauma. Postoperative retinal detachment developed in 3 of 52 (5.8%) eyes. The first of these was macula‐on and developed 13 days postoperatively and was due to an entry site break. In the second case, a macula‐on detachment presented 25 months postoperatively and was due to round holes in the lattice. In the third case, a retinal detachment developed 11 days postoperatively and was thought to be due to a macular hole induced at the time of CNV removal. In all three eyes retinal reattachment was achieved and VA was improved relative to baseline at last review (duration of follow‐up 48, 48 and 12 months).
Forty‐six eyes were phakic at the time of original vitrectomy. Excluding the eye with peroperative lens trauma necessitating peroperative lensectomy, four eyes underwent subsequent cataract surgery (mean follow‐up 42 months, range 24–60 months). The mean follow‐up time was similar for eyes requiring cataract surgery and for those which did not (42 vs 38 months). The mean age at the time of vitrectomy of patients who went on to require cataract surgery was 57.3 versus 36.6 years for those who did not require cataract surgery (p=0.014). No patient <40 years at the time of vitrectomy required cataract surgery with follow‐up up to 5 years. This included the four eyes which underwent repeat vitrectomy for visually significant recurrence of choroidal neovascularisation.
Worse baseline VA was correlated with improvement in VA (R=0.45, p=0.003, fig 22).). When acuity was considered as a dichotomous variable (ie, 6/30 or <6/30), worse baseline acuity was associated with a greater frequency of visual improvement (21/25 (84%) vs 5/16 (31%), p=0.001). After adjustment for differences in baseline VA, we found little evidence of any association between the magnitude of logMAR acuity change at 24 months and patient age (p=0.17), lesion size (p=0.21) and duration of surgery (p=0.65). Timing of surgery relative to onset of symptoms (p=0.74) and timing of surgery relative to timing of presentation (p=0.53) were not found to be associated with worse visual outcomes. The mean time to surgery from symptoms was quite long (25 weeks), with only two eyes having surgery within 4 weeks of symptoms. There was insufficient power to evaluate an association between improvement in acuity at 24 months and subfoveal lesion site, CNVM occult component, haemorrhage >50% of lesion, previous argon laser treatment, previous corticosteroid treatment or CNVM recurrence. Table 11 summarises the VA change relative to diagnosis. No significant association was observed between diagnosis and VA improvement.
The present study found that eyes undergoing surgical removal of non‐AMD‐related choroidal neovascular membranes had an 88% likelihood of having a same or better VA at 2 years. This was in the setting of a single‐centre, single‐clinician consecutive case series. Worse baseline VA was found to correlate with greater magnitude of visual improvement. No other factors were found to be associated with change in VA. We believe that VA can take some time to improve postoperatively. Indeed, in the present study, the mean change in acuity steadily rose from 1 to 4 years postoperatively (table 22).
Recurrent or persistent CNV was seen in 17 (33%) eyes, a figure comparable to other case series, although lower than the 58% in the submacular surgery trial (SST)‐H trial.10,11 This difference is likely due to the rigorous angiographic follow‐up in the SST and the fact that 10 (20%) eyes had <2 years follow‐up in the present study. Recurrent CNV remained untreated in 71% of cases in the present study, and did not seem to be associated with worse visual outcomes although the size of the present study was insufficient to properly evaluate this. Recurrences were often small, self‐limited and less visually significant than the original CNV (eg, fig 33).
Peripheral retinal breaks were noted at the time of surgery in a relatively high 10% of cases. This was similar to the figure reported in the submacular surgery trial (14/112, 12.5%). This rate of peripheral break formation is higher than that after macular hole surgery,12 and is thought to be inherent to the nature of the procedure. The authors postulate that this is due to the necessity for repeated insertion of relatively large, angled instruments (subretinal cannula, subretinal forceps).
Nuclear sclerotic cataract is a common complication of vitrectomy. The present study found that patients undergoing cataract surgery after vitrectomy were significantly older than those not requiring cataract surgery. Indeed, no patient <40 years of age at the time of vitrectomy required cataract surgery with follow‐up as long as 5 years. This is consistent with the findings of others.13,14,15 Oxidative lens damage the likely mechanism of postvitrectomy cataract formation.16,17 A younger lens probably has less baseline cumulative oxidative damage; therefore it is understandable that it might take longer for a cataract to develop postoperatively.
The visual outcomes in the present study are comparable to the reported results in other larger (n>50) case series of surgical removal of POHS‐related CNVM (table 33).10,11 The results of these studies and the present study are better than those of the POHS/idiopathic eyes in the SST‐H, which had a 55% frequency of successful outcome (same or better vision) at 2 years, but only a 27% frequency of improved vision.4 This may be due to the different populations of patients in the current study and in the SST. Indeed subgroup analysis in the SST showed a 76% success rate in the group with worse vision at baseline, a success rate not dissimilar to that of these other non‐randomised case series, suggesting that case selection can influence visual results. The present study population was from the UK, and the most common cause of the CNV was PIC. This is in contrast with the North American‐based SST, in which 85% of patients had POHS. Baseline VA was worse in the present study than in the SST. The SST showed that worse baseline acuities were associated with better outcomes—a trend we also observed in the present study. therefore, we might expect better overall visual outcomes.
Other treatments have been used for the treatment of type II choroidal neovascular membranes, including photodynamic therapy (PDT) and systemic corticosteroids. Rosenfeld et al18 noted an 82% frequency of same or better vision at 2 years in their uncontrolled, prospective, open‐label study of PDT with verteporfin for ocular histoplasmosis. Chan et al19 noted a 92% frequency of same or better vision at 12 months in a small prospective series of PDT with verteporfin for idiopathic CNV in a Chinese population (table 33).). All patients had good visual outcomes in the small phase 1 and 2 study of verteporfin treatment for non‐AMD‐related CNVM described by Sickenberg et al.23 There are a number of other smaller retrospective case series of PDT with verteporfin for non‐AMD‐related CNVM, and most of them also claim very good visual results.24,25,26,27,28,29,30,31 Postelmans et al,32 however, emphasise that PDT with verteporfin is not without its risks in these often young patients.
Systemic corticosteroids have been said to be beneficial in patients with choroidal neovascularisation secondary to PIC and multifocal choroiditis. Several retrospective case series describe good visual outcomes after steroid therapy,33,34,35 sometimes combined with PDT.36 There is histological evidence to support an inflammatory process being involved in angiogenesis in multifocal choroiditis, even in the absence of other signs of ocular inflammation.37
Many of these case series of therapies for type II choroidal neovascularisation, including those in the present study, are plagued by a lack of a control group against which to compare the treatment. It is important to note that generally the natural history of type II CNVM is better than that for AMD (table 33).). Although the natural history of subfoveal CNVM is now well documented in POHS4 and myopia,20 and to a lesser degree for idiopathic membranes,21 there is little natural history data for CNVM related to PIC and multifocal choroiditis. To date the only proved treatment for subfoveal CNVM due to POHS or idiopathic is surgery, with demonstrated efficacy in patients with acuities worse than 20/100.
The present study has shown the safety of surgery for non‐AMD‐related subfoveal CNVM in a UK population, and supports the notion that surgery be considered particularly for those with an acuity of 6/36 or worse.
AMD - age‐related macular degeneration
CNV - choroidal neovascularisation
CNVM - choroidal neovascular membranes
PIC - punctate inner choridopathy
POHS - periodical occupational health survey
SST - submacular surgery trial
Competing interests: None declared.
Data previously presented at ARVO 2005 as a poster, 4 May 2005.