Retinal findings in patients with COVID-19: Results from the SERPICO-19 study.

BACKGROUND: Coronavirus disease 2019 (COVID-19) has been associated to microvascular alterations. We screened the fundus of patients with COVID-19 to detect alterations of the retina and its vasculature and to assess possible correlations with clinical parameters. METHODS: Cross-sectional study. The presence of retinal alterations in patients with COVID-19 and subjects unexposed to the virus was assessed using fundus photographs and their prevalence was compared. Mean arteries diameter (MAD) and mean veins diameter (MVD) were compared between patients and unexposed subjects with multiple linear regression including age, sex, ethnicity, body mass index, smoking/alcohol consumption, hypertension, hyperlipidaemia, diabetes as covariates. The influence of clinical/lab parameters on retinal findings was tested in COVID-19 patients. FINDINGS: 54 patients and 133 unexposed subjects were enrolled. Retinal findings in COVID-19 included: haemorrhages (9·25%), cotton wools spots (7·4%), dilated veins (27·7%), tortuous vessels (12·9%). Both MAD and MVD were higher in COVID-19 patients compared to unexposed subjects (98·3 ± 15·3 µm vs 91·9 ± 11·7 µm, p = 0.006 and 138·5 ± 21·5 µm vs 123·2 ± 13·0 µm, p<0.0001, respectively). In multiple regression accounting for covariates MVD was positively associated with COVID-19 both in severe (coefficient 30·3, CI95% 18·1-42·4) and non-severe (coefficient 10·3, CI95% 1·6-19·0) cases compared to unexposed subjects. In COVID-19 patients MVD was negatively correlated with the time from symptoms onset (coefficient -1·0, CI 95% -1·89 to -0·20) and positively correlated with disease severity (coefficient 22·0, CI 95% 5·2-38·9). INTERPRETATION: COVID-19 can affect the retina. Retinal veins diameter seems directly correlated with the disease severity. Its assessment could have possible applications in the management of COVID-19. FUNDING: None.

Large Idiopathic Macular Hole Surgery: Remodelling of Outer Retinal Layers after Traditional Internal Limiting Membrane Peeling or Inverted Flap Technique.

OBJECTIVE: To investigate the influence of the inverted flap technique compared with traditional internal limiting membrane (ILM) peeling in the postoperative remodelling of outer retinal layers of idiopathic macular holes (MHs) >450 µm. METHODS: We analyzed medical records and imaging studies of all patients with an idiopathic MH >450 µm who underwent vitrectomy at the Sacco University Hospital, Milan, and the Sacro Cuore Don Calabria Hospital, Verona, Italy, between January 2008 and December 2017. Out of 41 eyes evaluated, 17 were treated with traditional ILM peeling and 24 with the inverted ILM flap technique. All patients underwent follow-up examinations every 3 months and all of them completed a final visit 12 months after surgery. Best-corrected visual acuity (BCVA) and optical coherence tomography (OCT) parameters were evaluated at each visit. The main outcome measures were the postoperative recovery rate of the external limiting membrane (ELM) and ellipsoid zone (EZ), and postoperative BCVA. Correlations between OCT measurements and visual outcome were analyzed. RESULTS: The ELM recovery rate in the ILM peeling group (15/17 eyes, 88%) was higher than in the ILM flap group (14/24 eyes, 58%) (p = 0.079). The EZ recovery rate was similar in the 2 groups, 7/17 eyes (41%) in the ILM peeling and 8/24 eyes (33%) in the ILM flap group (p = 0.744). Eyes without a persistent hyper-reflective "plug" at the edges of the MH showed a significantly higher EZ recovery rate (11/18, 61%) compared with eyes showing a persistent plug (4/23, 17%) (p = 0.008). The mean BCVA improved significantly in both groups: from 0.93 logMAR (20/170) to 0.26 logMAR (20/36) in the ILM peeling and from 0.98 logMAR (20/190) to 0.37 logMAR (20/46) in the ILM flap group. The final BCVA tended to be better in the ILM peeling group (p = 0.085). CONCLUSIONS: Given the limited information about the influence of ILM flap versus traditional ILM peeling in the postoperative remodelling of large idiopathic MHs, our data provides some new insights into the healing process of MHs >450 µm. This should be considered as part of the decision process about whether to perform an ILM flap in these patients.

The Incidence of Neovascularization in the Fellow Eye of Patients with Unilateral Choroidal Lesion: A Survival Analysis.

PURPOSE: To compare the difference in the rate of survival of unaffected fellow eyes between choroidal neovascularization (CNV) in the first eyes and retinal angiomatous proliferation (RAP) in the first eyes. DESIGN: Cohort retrospective study. PARTICIPANTS: A total of 329 consecutive patients enrolled in our Eye Clinic between February 2006 and November 2014 were involved in the study. Only patients with naïve unilateral forms of neovascularization in 1 eye were included in this study. METHODS: A clinical database containing patients' data and ocular history was evaluated. Only patients with naive lesions in 1 eye and without signs of neovascular AMD in the fellow eye were included in the analysis. The time of absence of neovascularization in the fellow eye was calculated. MAIN OUTCOME MEASURES: Survival of the fellow eye was estimated by Kaplan-Meier analysis, and log-rank test was used to compare CNV and RAP fellow eye survival. RESULTS: A total of 202 eyes affected by CNV and 39 eyes affected by RAP were enrolled in the study. The mean follow-up time was 2.9 years (range, 182-2461 days) for CNV and 2.6 years (range, 519-1504 days) for RAP. Kaplan-Meier analysis showed that the 50% of the fellow eyes with CNV did not develop neovascularization for 5.3 years, whereas the 50% of the fellow eyes with RAP did not develop neovascularization for 3.5 years. Log-rank test showed a highly significant difference between the 2 curves (P < 0.002). CONCLUSIONS: This study showed that the incidence of neovascularization in the unaffected fellow eye increases with time, and when the first eye is affected by RAP, the development of a lesion in the second eye is more premature.

The absence that makes the difference: choroidal abnormalities in Legius syndrome.

Neurofibromatosis type 1 (NF1) is an hereditary disorder characterized by abnormal proliferation of multiple tissues of neural crest origin, and presents mainly with multiple café-au-lait macules, axillary freckling and neurofibromas. Choroidal involvement in NF1 patients has been studied, thanks to the development of non-invasive tools such as infrared monochromatic light during fundus examination, which showed bright patchy lesions consistent with choroidal nodules. Choroidal abnormalities identified with near-infrared reflectance have reported with a frequency of up to 100% in NF1, and have been recently been proposed as a novel diagnostic criterion for NF1. Legius syndrome can be clinically indistinguishable from NF1 and results in a small percentage of individuals being misdiagnosed. We investigated the presence of choroidal abnormalities in Legius syndrome to determine their specificity to NF1 and their potential usefulness as a novel diagnostic criterion for NF1. We examined the fundus of 16 eyes by confocal scanning laser ophthalmoscopy with infrared monochromatic light in eight patients with molecularly confirmed Legius syndrome. No abnormalities were observed, confirming the diagnostic value of choroidal abnormalities for the diagnosis of NF1.

RETINAL ANGIOMATOUS PROLIFERATION DIAGNOSIS: A Multiimaging Approach.

PURPOSE: To identify signs occurring more frequently in retinal angiomatous proliferation (RAP) lesions compared with other types of choroidal neovascularization (CNV) in age-related macular degeneration. METHODS: In this cross-sectional retrospective study, 30 patients were evaluated. These signs were correlated with the type of CNV: shunting of blood flow to the lesion by fluorescein angiography, late leakage by indocyanine green angiography, intraretinal cysts and retinal pigmented epithelium interruption along the retinal pigmented epithelium detachment with a hyperreflective oval area by spectral domain optical coherence tomography, and presence of reticular pseudodrusen by infrared light. RESULTS: Shunting of blood flow was found in 56% of RAP, whereas it was absent in 100% of other CNVs. Late leakage in indocyanine green angiography occurred in all RAP cases, while it was found in 7% of other CNVs. Intraretinal cysts were detected in 100% of RAP cases and in 14% of other CNVs. Retinal pigmented epithelium interruption along the retinal pigmented epithelium detachment was evident in 93% of RAP cases and in 15% of other CNVs. Reticular pseudodrusen were present in 87% of RAP cases and in 21% of other CNVs. CONCLUSION: All the signs investigated were strongly associated to RAP lesions. A multimodal imaging approach may help differentiating subtypes of neovascularization.

Re-accumulation of macular pigment after successful macular hole surgery.

AIMS: To investigate macular pigment optical density (MPOD) during follow-up of sealed macular holes and to study correlations of MPOD with progressive changes in spectral-domain optical coherence tomography (SD-OCT) and functional results. METHODS: Consecutive patients (n=18) who had undergone successful vitrectomies for idiopathic macular holes were evaluated postoperatively at 1, 3, 6 and 9 months. At each follow-up visit, MPOD was measured with a modified confocal scanning laser ophthalmoscope and the outer retina evaluated by SD-OCT. The changes of MPOD postoperatively and the relationship of MPOD and SD-OCT findings to best corrected visual acuity were examined. RESULTS: MPOD did not change significantly throughout follow-up, from 0.49±0.22 (mean±SD) at month 1 to 0.42±0.18 at month 9. There was a tendency towards a significant association between amount of MPOD and recovery of external limiting membrane during follow-up (p=0.068). Best corrected visual acuity increased significantly from 0.24±0.12 before surgery to 0.65±0.25 at month 9. Recovery of the ellipsoid zone determined most of visual acuity improvement (p=0.024). MPOD was not associated with visual acuity changes (p=0.394). CONCLUSIONS: Revisualisation of macular pigment after successful macular hole surgery is not associated with improved visual acuity and may merely be an accompanying sign of the reapposition of the edges of the hole.

Diabetic retinopathy screening: the first telemedical approach in an Italian hospital.

PURPOSE: To assess the feasibility of a telemedical approach for diabetic retinopathy (DR) screening in the Italian population and to evaluate advantages/disadvantages in comparison to standard slit-lamp funduscopic examination (SFE). METHODS: This 1-year, Italian, single-center, observational study evaluated semiautomatic fundus photography (FP) DR screening, performed during routine type 2 diabetes (T2D) systemic visits and examined remotely. Adults with T2D underwent SFE and 3-field FP. The study was divided into 2 stages (stage 1 validated the screening procedure, stage 2 evaluated the screening impact on the clinical practice). Annual costs of SFE ± FP screening were compared. Patients completed a DR screening questionnaire. RESULTS: Of 1,281 T2D patients enrolled, 61% were male (mean age 65.69 ± 12.64 years). In stage 1, 71% and 15% of patients were considered nongradable when FP was performed before (BPD) versus after pupil dilation (APD). The FP specificity was higher with APD vs BPD (79% vs 25%); therefore, FP APD only was used for stage 2. Of 1,281 patients screened using FP APD, 240 (18.7%) had unreadable images; 64.3% did not have DR, and 17.0% were diagnosed with DR. There was a cost saving of €801.25 when screening was performed using FP. Overall, 98% of patients had a positive opinion of FP screening. CONCLUSIONS: The telemedicine approach provides a convenient, simple test that is well-received by patients and minimizes unnecessary referrals. Telemedicine may also reduce screening costs in our setting.

Choroidal granulomas visualized by enhanced depth imaging optical coherence tomography.

PURPOSE: To assess the visualization of choroidal granulomas (CG) by enhanced depth imaging optical coherence tomography (EDI-OCT) and to describe their EDI-OCT characteristics. METHODS: Combined indocyanine green (ICG) angiography and EDI-OCT images of 44 CG (sarcoid, tubercular, or Vogt-Koyanagi-Harada related) were reviewed. By ICG angiography, CG were classified as full thickness or partial thickness and as small or large. Two independent operators evaluated EDI-OCT scans over granulomas to record their characteristics (full thickness/partial thickness, shape, reflectivity, internal pattern, margins, and shadowing/increased transmission effect). The agreement between ICG angiography and EDI-OCT, the interobserver agreement, and the correlations between EDI-OCT features and lesion size or disease were studied. RESULTS: Enhanced depth imaging optical coherence tomography could visualize 100% of CG detected on ICG. Lesions resulted full thickness in 90.9% and 77.3% of the cases on ICG angiography and EDI-OCT, respectively (K = 0.5). All CG were more homogeneous and showed increased transmission of the optical coherence tomography signal as compared with the surrounding choroid. Choroidal granulomas angiographic size influenced lesions characteristics on EDI-OCT. Large granulomas were more likely to be full thickness, round shaped, with defined margins, lower reflective than the surrounding structures, and with internal homogenous pattern. The type of disease significantly influenced CG shape and pattern. Most of tubercular-related lesions showed lobulated shape and nonhomogeneous internal pattern. CONCLUSION: Enhanced depth imaging optical coherence tomography is suitable to visualize CG and to describe their characteristics. Choroidal granulomas size and disease influence lesions appearance on EDI-OCT. Increased transmission effect could be helpful for CG identification.

Intravitreal bevacizumab for choroidal neovascularization secondary to angioid streaks: a long-term follow-up study.

PURPOSE: To evaluate the safety and efficacy of intravitreal bevacizumab (IVB) to treat choroidal neovascularization (CNV) in patients with angioid streaks. METHODS: Retrospective chart review of 16 eyes of 10 patients treated with IVB for CNV secondary to angioid streaks between November 2005 and November 2011. Intravitreal bevacizumab was performed in all patients with a pro re nata regimen. Seven eyes received an additional photodynamic therapy and 1 eye argon laser photocoagulation. The diagnosis of CNV was confirmed by fluorescein angiography (FA) and indocyanine green (ICG) angiography; central macular thickness (CMT) was evaluated by optical coherence tomography. Outcome measures included changes in best-corrected visual acuity, retinal thickness, and degree of leakage on FA and ICG angiography. RESULTS: The median number of IVB was 2.5 (range 1-6) during a mean follow-up of 52 months (range 30-67). Risk of recurrence increased during the first 50 weeks; then it remained stable. In 6 of 16 eyes, the CNV was obliterated with a single injection. Increasing CNV reactivation corresponded with an increased number of injections. Final visual acuity was related to initial VA and not to number of injections or shorter follow-up. Previous treatments, CMT, or baseline CNV size were not related to final visual acuity. CONCLUSIONS: Intravitreal bevacizumab proved to be well-tolerated in patients with CNV secondary to angioid streaks and in our small cohort IVB was efficacious for long-term follow-up. Larger series of patients are needed to confirm the effects of this treatment.

Spectral-domain optical coherence tomography as an indicator of fluorescein angiography leakage from choroidal neovascularization.

PURPOSE: To evaluate spectral-domain optical coherence tomography (SD-OCT) findings that predict angiographic leakage in choroidal neovascularization (CNV). METHODS: SD-OCT and fluorescein angiography (FA) images of 93 eyes of 93 patients were retrospectively analyzed. All patients were previously treated with anti-vascular endothelial growth factor agents for CNV from age-related macular degeneration. FA images were analyzed to assess the presence of leakage. SD-OCT images were analyzed to identify the overall presence of fluid, as well as specific patterns of fluid presentation, including intraretinal cystic spaces (ICS), retinal pigment epithelium detachment (PED), and neurosensory detachment (NSD). The presence of ultrastructural features such as intraretinal hyperreflective flecks and the inherent reflectivity and boundary definition of the subretinal material were evaluated. Both the association and the sensitivity, specificity, and both positive and negative predictive values of SD-OCT findings compared with FA leakage were calculated. RESULTS: A statistically significant association between SD-OCT findings and FA leakage was found for eyes that displayed fluid, NSD, intraretinal flecks, and low reflectivity or undefined boundaries from subretinal material, and not for PED or ICS. Sensitivity and specificity for SD-OCT findings were, respectively: 94% and 27% for fluid; 68% and 88% for NSD; 81% and 83% for intraretinal flecks; 63% and 92% for undefined boundaries of subretinal material; and 94% and 87% for low reflectivity from subretinal material. CONCLUSIONS: The evidence of fluid on SD-OCT is sensitive but nonspecific in identifying FA leaky CNV. The assessment of neurosensory detachment as well as other ultrastructural elements may increase the specificity of analysis.

Displayed reflectivity of choroidal neovascular membranes by optical coherence tomography correlates with presence of leakage by fluorescein angiography.

PURPOSE: To evaluate and correlate the displayed optical reflectivity of choroidal neovascularization (CNV) subretinal material on spectral-domain optical coherence tomography with the presence of dye leakage on fluorescein angiography (FA). METHODS: Thirty-nine eyes of 39 patients with a diagnosis of predominantly classic CNV from age-related macular degeneration underwent simultaneous spectral-domain optical coherence tomography and FA imaging. Eight patients had a newly diagnosed untreated CNV. Thirty-one patients had already been treated with anti-vascular endothelial growth factor agents. In 18 of these eyes, CNV lesions showed persistent leakage on FA. In 13 eyes, CNV lesions did not show leakage by FA. Subretinal CNV material boundaries visualized on spectral-domain optical coherence tomography B-scans were manually traced, and optical reflectivity was calculated using the mean grayscale value. To account for variable image brightness, the retinal pigment epithelial reflectivity was measured. The absolute difference between CNV material and retinal pigment epithelial reflectivity (ΔREF) from the three groups (newly diagnosed CNV, previously treated CNV showing FA leakage, and previously treated CNV not showing FA leakage) was compared. RESULTS: In untreated lesions, ΔREF was significantly higher compared with previously treated, but still leaky CNV (P < 0.0001). Lesions showing FA leakage had significantly higher ΔREF compared with those that did not display leakage (P < 0.0001). CONCLUSION: The displayed reflectivity of subretinal CNV material in spectral-domain optical coherence tomography appears to be an important parameter that can provide information regarding the FA leakage status.

The dynamic healing process of idiopathic macular holes after surgical repair: a spectral-domain optical coherence tomography study.

PURPOSE: To analyze progressive changes of the outer retina after vitrectomy for macular hole (MH) repair. METHODS: Nineteen consecutive patients underwent vitrectomy for idiopathic MH. Spectral domain optical coherence tomography (SD-OCT) examinations were performed pre- and postoperatively during follow-up visits at 1, 3, 6, 9, and 12 months. Active eye-tracking technology ensured that the same scanning location was identified each time. RESULTS: Ten eyes showed a normal external limiting membrane (ELM) at 1 month after surgery and 15 eyes at 3 months. The ELM was already continuous in 79% of the eyes with persistent outer foveal defects during follow-up. No eyes revealed a continuous inner segment/outer segment (IS/OS) line at 1 month, only one eye at 3 months, and 10 eyes at 12 months. No eyes had a disrupted ELM with an intact IS/OS line. Foveal cysts were visible in three eyes at 1 month and in eight eyes during follow-up. The cystic space gradually filled, resulting in a continuous IS/OS line in five of these eyes. Recovery of ELM, IS/OS, and outer nuclear layer (ONL) determined most of visual acuity improvement. The ONL appeared normal in the 10 eyes with an intact IS/OS line at last follow-up. By contrast, it was disrupted in 7 of 9 eyes with a final persistent outer foveal defect. CONCLUSIONS: The ELM is the first structure to recover after MH closure. Foveal cysts may develop during follow-up, and in the presence of an intact ONL, they may gradually fill with complete recovery of the IS/OS junction.

Reproducibility of retinal thickness measurements on normal and pathologic eyes by different optical coherence tomography instruments.

PURPOSE: To compare retinal thickness measurements produced by different time-domain and spectral-domain optical coherence tomography (TD-OCT and SD-OCT) devices when imaging normal and pathologic eyes. DESIGN: Prospective, observational study in an academic institutional setting. METHODS: A total of 110 eyes were imaged by 6 different OCT devices: Stratus and Cirrus (Carl Zeiss Meditec Inc), Spectralis HRA+OCT (Heidelberg Engineering), RTVue-100 (Optovue Inc), SDOCT Copernicus HR (Optopol Technology S.A.), and 3D OCT-1000 (Topcon Corporation). Eyes were normal or affected by different pathologies of the retina, including exudative and nonexudative age-related macular degeneration, epiretinal membrane, cystoid macular edema, and macular hole. For each instrument we used standard analysis protocols for macular thickness evaluation. Mean retinal thickness values between the instruments in the ETDRS central circular 1000-µm-diameter areas and in the ETDRS midperipheral circular 3000-µm-diameter areas were compared. RESULTS: The 6 different devices produced measurements that differ in variance (Bartlett test, P = .006), and mean values (Friedman test, P < .001). Bland-Altman analysis revealed that the limits of agreement for all the comparisons were not acceptable. Regression was calculated and it was elaborated into a conversion table, despite a high standard error for both intercepts and slope conversion values. CONCLUSIONS: This study suggests that retinal thickness measurements obtained with various OCT devices are different beyond clinical practice tolerance, according to Bland-Altman analysis. Furthermore, regression analysis reveals high standard error values. These differences appear to be primarily attributable to the analysis algorithms used to set retinal inner and outer boundaries.

Artifacts in automatic retinal segmentation using different optical coherence tomography instruments.

PURPOSE: The purpose of this study was to compare and evaluate artifact errors in automatic inner and outer retinal boundary detection produced by different time-domain and spectral-domain optical coherence tomography (OCT) instruments. METHODS: Normal and pathologic eyes were imaged by six different OCT devices. For each instrument, standard analysis protocols were used for macular thickness evaluation. Error frequencies, defined as the percentage of examinations affected by at least one error in retinal segmentation (EF-exam) and the percentage of total errors per total B-scans, were assessed for each instrument. In addition, inner versus outer retinal boundary delimitation and central (1,000 microm) versus noncentral location of errors were studied. RESULTS: The study population of the EF-exam for all instruments was 25.8%. The EF-exam of normal eyes was 6.9%, whereas in all pathologic eyes, it was 32.7% (P < 0.0001). The EF-exam was highest in eyes with macular holes, 83.3%, followed by epiretinal membrane with cystoid macular edema, 66.6%, and neovascular age-related macular degeneration, 50.3%. The different OCT instruments produced different EF-exam values (P < 0.0001). The Zeiss Stratus produced the highest percentage of total errors per total B-scans compared with the other OCT systems, and this was statistically significant for all devices (P < or = 0.005) except the Optovue RTvue-100 (P = 0.165). CONCLUSION: Spectral-domain OCT instruments reduce, but do not eliminate, errors in retinal segmentation. Moreover, accurate segmentation is lower in pathologic eyes compared with normal eyes for all instruments. The important differences in EF among the instruments studied are probably attributable to analysis algorithms used to set retinal inner and outer boundaries. Manual adjustments of retinal segmentations could reduce errors, but it will be important to evaluate interoperator variability.

Treatment of retinal angiomatous proliferation in age-related macular degeneration: a series of 104 cases of retinal angiomatous proliferation.

OBJECTIVE: To report the management of retinal angiomatous proliferation (RAP), a recently described intraretinal neovascular lesion occurring in age-related macular degeneration. METHODS: This was a retrospective review of consecutive patients with age-related macular degeneration who underwent treatment of RAP from January 1, 2000, through January 31, 2003. Inclusion criteria were age 55 years or older, signs of age-related macular degeneration, and diagnosis of RAP based on dynamic indocyanine green angiography. Baseline angiograms were reviewed and RAP was classified into the following 3 stages: stage 1, intraretinal neovascularization, early stage; stage 2, subretinal neovascularization, middle stage; and stage 3, choroidal neovascularization, late stage. Treatment and concomitant treatment results were assessed separately for each RAP stage. The clinical data were statistically analyzed (chi2 test and analysis of variance) for 2 main outcome measures--complete obliteration of the lesion and final visual acuity. RESULTS: Eighty-one patients (99 eyes) with 104 RAPs were identified. Forty-two lesions were at stage 1, 42 at stage 2, and 20 at stage 3. The following 5 treatments were performed: direct laser photocoagulation of the vascular lesion, laser photocoagulation of the feeder retinal arteriole, scatter "gridlike" laser photocoagulation, photodynamic therapy, and transpupillary thermotherapy. Complete obliteration of RAP was achieved in about 24 (57.1%) of the stage 1 lesions (direct laser photocoagulation of the vascular lesion, 73% success rate; photodynamic therapy, 45%), 11 (26.2%) of the stage 2 lesions (scatter gridlike laser photocoagulation, 38% success rate; direct laser photocoagulation of the vascular lesion, 17%), and only 3 (15.0%) of stage 3 lesions (P = .001). Predictive factors with a significant effect on final visual acuity were initial visual acuity (P = .003) and early lesion stage (P = .04). Best final visual acuity was 0.41 (mean, direct laser photocoagulation of the vascular lesion in stage 1) and 0.39 (mean, photodynamic therapy in stage 1), with a mean decrease of 2.5 and 3 lines from baseline, respectively. CONCLUSIONS: Treatment of RAP remains difficult. Early detection of the lesion and subsequent direct conventional laser photocoagulation seems to be associated with better anatomical and functional outcome. Once the vascular complex is well established, anatomical closure is rarely achieved. Further study is warranted to assess the long-term efficacy and the need for re-treatment.