To evaluate preoperative and postoperative retinal function in patients who underwent macular surgery for idiopathic macular hole.
Prospective, comparative, interventional case series.
Thirty eyes of 30 patients with idiopathic macular hole were included in the study. Patients underwent pars plana vitrectomy and peeling of the internal limiting membrane (ILM). ILM visualization was improved in 15 patients by using triamcinolone acetonide and in the remaining 15 patients by using infracyanine green dye. Spectral-domain optical coherence tomography examination was performed to document macular hole closure. Retinal function was assessed preoperatively and postoperatively over a period of 12 months by best-corrected visual acuity (BCVA) measurement (ETDRS chart), MP-1 microperimetry, and focal electroretinogram recording (fERG). Focal electroretinograms were recorded in response to a sinusoidally modulated (41 Hz), uniform field presented to the macular (18 degrees) and foveal (2.25 degrees) region.
Macular hole closure was achieved in all patients in both groups. At 12 months, visual acuity improved in both groups ( P < .001), and there were no statistically significant differences between groups. Mean macular sensitivity within the central 2 and 8 degrees increased in both groups, and there were no statistically significant differences between groups at any follow-up. In the triamcinolone acetonide group, 12 months after surgery the amplitude of the fERG’s first harmonic (1F) increased both in the macular region ( P < .001) and in the foveal region ( P < .05). In the infracyanine green group, at 12 months the amplitude of the first harmonic (1F) decreased in both areas. The decrease was significant in the macular region ( P < .05) and not significant in the foveal region ( P = .095).
Vitrectomy and ILM peeling assisted with either triamcinolone acetonide or infracyanine green staining improves visual acuity and mean macular sensitivity at 12 months in patients affected by idiopathic macular hole. However, triamcinolone acetonide staining is associated with an increase of fERG’s first harmonic amplitude in the foveal and macular region, whereas in the case of infracyanine green staining it seems to decrease after surgery. The reduction of the amplitude of fERG’s first harmonic suggests that infracyanine green may have a late toxic effect on photoreceptor cells.
The first paper reporting successful surgical treatment for idiopathic macular hole was published by Kelly and Wendel in 1991. The surgery consisted of pars plana vitrectomy with a gas-fluid exchange. Since then, macular hole surgery has evolved, with improved anatomic and functional outcomes. Internal limiting membrane (ILM) peeling was introduced by Eckardt and associates in 1997. The addition of this technique improved the closure rate of macular holes compared with vitrectomy and gas alone. However, visualization of the ILM is difficult, and its removal may lead to visual field defects and retinal pigment epithelium (RPE) damage.
Indocyanine green (ICG) staining of the ILM was introduced to improve visualization and facilitate ILM removal, but reports about the possible toxicity of ICG led researchers to look for safer, alternative dyes. Triamcinolone acetonide, bromophenol blue, brilliant blue, trypan blue, and infracyanine green have all been investigated. However, most of the in vivo studies on the potential retinal toxicity of these dyes have evaluated visual acuity alone.
In this study we performed a 12-month evaluation of macular and foveal function in patients after pars plana vitrectomy and ILM peeling assisted by intravitreal injection of triamcinolone acetonide or infracyanine green for idiopathic macular holes. Macular and foveal function were assessed pre- and postoperatively, over a period of 12 months, by visual acuity measurement, MP-1 microperimetry, and focal electroretinography.
In this prospective observational case series, 30 eyes of 30 patients underwent transconjunctival pars plana vitrectomy and ILM peeling for idiopathic, full-thickness macular holes (stage II-IV of Gass’ classification). The study was approved by the Ethics Committee of the Catholic University of Rome and all patients consented to participate in this research study as well as for surgery.
Eleven male and 19 female subjects with ages ranging from 49 to 74 years (mean ± SD, 64.6 ± 6.3 years) were enrolled. The diagnosis and staging of macular holes as well as closure and anatomic changes postoperatively were made by slit-lamp fundus examination and spectral-domain optical coherence tomography (OCT) (Cirrus OCT; Carl Zeiss Meditec, Inc, Dublin, California, USA). Ten patients had stage II, 16 patients had stage III, and 4 patients had stage IV macular holes. In the first 15 patients, triamcinolone acetonide was used to visualize the ILM, while in the remaining 15 patients infracyanine green was used to stain the ILM ( Table ). Exclusion criteria were visual acuity worse than 1.0 (logMAR), previous macular surgery, corneal opacities, macular diseases other than macular hole, optic nerve atrophy, or any coexistent disease that was likely to compromise the anatomic or functional outcome. Phakic patients were excluded to avoid the possible interference of lens opacities with functional tests.
|Triamcinolone Acetonide||Infracyanine Green||P Value a|
|Number of eyes||15||15|
|Mean age ± SD||65.1 ± 6.6||64.2 ± 6.3|
|Macular hole stage|
|Macular hole minimum diameter (mean ± SD)||316 ± 180 μm||331 ± 183 μm|
|Macular hole base diameter (mean ± SD)||717 ± 231 μm||727 ± 223 μm|
|Macular hole index||0.601 ± 0.213||0.573 ± 0.207|
|Duration of symptoms (months)||5.5 ± 2.2||5.7 ± 1.9|
|BCVA (logMAR) (mean ± SD)||0.60 ± 0.23||0.52 ± 0.22||.84|
|FERG first harmonic (macular) (mean ± SD)||1.74 ± 0.84 μV||1.73 ± 1.09 μV||.99|
|FERG first harmonic (foveal) (mean ± SD)||0.52 ± 0.16 μV||0.51 ± 0.27 μV||.95|
|MP-1 central 2 degrees (mean ± SD)||10.54 ± 3.58 dB||9.75 ± 5.03 dB||.98|
|MP-1 central 8 degrees (mean ± SD)||13.55 ± 3.22 dB||12.36 ± 5.13 dB||.93|
Retinal function was assessed in all patients preoperatively and postoperatively, over a period of 12 months. ETDRS best-corrected visual acuity (BCVA) was recorded preoperatively, and at 7 days and 1, 3, 6, and 12 months postoperatively. For statistical analysis, visual acuity results were converted to logMAR units. Nidek MP-1 microperimetry (Nidek Technologies, Vigonza, Italy) was carried out preoperatively and at 1, 3, 6, and 12 months postoperatively. Focal electroretinograms (fERG) were recorded preoperatively and at 7 days and 1, 3, 6, and 12 months postoperatively.
All procedures were performed by a single surgeon (A.S.). Surgery consisted of standard 25-gauge pars plana vitrectomy and separation and removal of the posterior hyaloid. In the triamcinolone acetonide group a volume of 0.2 mL triamcinolone acetonide (40 mg/mL; Kenalog, Bristol-Myers Squibb, Anagni, Italy) was injected into the vitreous cavity to visualize the internal limiting membrane. In the other group ILM staining was performed using infracyanine green with the following procedure: Infracyanine green (25 mg) (SERB Laboratories, Paris, France) was dissolved in 10 mL 5% dextrose solution. This solution was further diluted 1:4 with balanced salt solution to obtain a final infracyanine green concentration of 0.5 mg/mL, 0.05% (308 mOsm). A volume of 0.2-0.3 mL of this final solution was used over the macula to stain the ILM. In both groups, excessive dye was removed after a few seconds from the vitreous cavity using the vitreous cutter before proceeding with ILM peeling. The ILM was peeled using Eckardt forceps. The peripheral retina was checked carefully for any iatrogenic, peripheral retinal breaks, after which a fluid-air exchange and injection of 20% sulfur hexafluoride was then performed. Postoperatively, all patients were kept in a face-down position for 7 days to facilitate macular hole closure.
Microperimetry was performed using the Nidek MP-1 device (Nidek Technologies, Vigonza, Italy) through a dilated pupil. A Goldmann I standard-size stimulus was used with a stimulus duration of 200 msec. The fixation target was a red cross whose size was varied according to the patient’s visual acuity and/or macular scotoma (range, 1-10 degrees). The location and stability of central fixation were determined by the patients’ ability to fixate on the chosen target for 20 seconds. The resulting fixation was then classified using Fujii’s method. A white, monochromatic background of 1.27 cd/m 2 was used, and a 4-2-1 double-staircase strategy was applied. In each patient, 5-minute visual adaptation and training were performed before the test. An automatic protocol was used with a customized radial grid to test 45 points covering the central 8 degrees. An automatic follow-up protocol was performed at each control examination, selecting the same retinal landmark as in the baseline evaluation. Macular sensitivity was defined as the mean retinal sensitivity of the central 8-degree area. Foveal sensitivity was defined as the mean of the points covering the central 2-degree area.
Focal electroretinograms were recorded monocularly, through a dilated pupil, by an Ag-AgCl electrode taped on the skin over the lower eyelid. A similar electrode, placed over the eyelid of the contralateral patched eye, was used as reference (interocular electroretinogram). The fERG signals were amplified, filtered (band pass-filter between 1 and 250 Hz, 6 dB/oct), and averaged (12-bit resolution, 2 kHz sampling rate, 1600 repetitions in 8 blocks). The sweep duration was kept equal to the stimulus period. Single sweeps exceeding the threshold voltage (25 μV) were rejected to minimize noise coming from blinks or eye movements. A discrete Fourier analysis was performed off line to isolate the fERG’s first harmonic, whose peak-to-peak amplitude was measured. Averaging and Fourier analysis were also performed on signals sampled asynchronously at 1.1 times the temporal frequencies of the stimuli to estimate the background noise at the stimulus frequencies. Under these experimental conditions, the fERGs recorded were above the noise level (noise amplitude ≤ 0.08 μV in all cases) and sufficiently reliable (the variation coefficient in amplitude was 20%).
Stimuli consisted of flickering uniform fields generated by an array of 8 red light-emitting diodes (LEDs; max lambda, 660 nm; half-height bandwidth, 25 nm; mean luminance, 80 cd/m 2 ) sinusoidally driven by a custom-made digital frequency generator and presented on the rear of a ganzfeld bowl (Primus; LACE Elettronica, Pisa, Italy) illuminated at the same mean luminance as the stimulus. A diffusing filter placed in front of the LED array made it appear as a circle of uniform red light. A steady DC signal maintained the mean luminance of the stimulus. fERGs were recorded in response to a sinusoidal luminance modulation (92% modulation depth) of 2 different homogeneous fields presented to the macular region: a circular area whose diameter subtended 2.25 degrees of visual angle (for foveal region assessment), obtained by applying to the entire field an annular white filter; and an outer annular region whose diameter subtended 18 degrees of visual angle (for macular region assessment).
A small central marker allowed the investigator to maintain steady fixation on the foveal region. The fixation distance was 30 cm for all patients. The stimulus temporal frequency was 41 Hz.
Each study group was analyzed by comparing the preoperative values of BCVA, MP-1 microperimetry sensitivity, and fERG’s first harmonic amplitude with the postoperative values measured at all follow-up time points. We also compared the preoperative and postoperative values of these parameters between the 2 study groups. These comparisons were based on analysis of variance and the Student-Newman-Keuls post hoc test. STATISTICA 7.0 software was used (Statsoft, Tulsa, Oklahoma, USA). For all analyses P < .05 values were considered statistically significant.
Patients in the 2 study groups were matched for age, duration of symptoms, and stage, index, and size of the macular hole. Preoperatively, there were no significant differences in BCVA, foveal or macular fERG amplitude, or MP-1 microperimetry sensitivity in the central 2 degrees and 8 degrees between groups ( Table ).
Anatomic success was achieved in all eyes, with macular hole closure documented by OCT examination.
Preoperative BCVA was 0.52 ± 0.22 in the infracyanine green group and 0.60 ± 0.23 in the triamcinolone acetonide group. Seven days after surgery, visual acuity decreased to 0.65 ± 0.19 in the infracyanine green group ( P = .0009) and remained stable in the triamcinolone acetonide group (0.58 ± 0.23, P = .68). At 30 days BCVA improved in both the infracyanine green and the triamcinolone acetonide groups (0.42 ± 0.19, P = .0086, and 0.31 ± 0.17, P = .0001, respectively). Visual acuity further increased throughout the follow-up in both groups. Twelve months after surgery, visual acuity improved to 0.27 ± 0.13 in the infracyanine green group ( P = .0001) and to 0.20 ± 0.18 in the triamcinolone acetonide group ( P = .0001).
No significant difference was found between the 2 groups at any follow-up ( Figure 1 ).
Preoperatively, microperimetry showed an absolute scotoma corresponding to the macular hole and a surrounding area of relative scotoma in all cases. In all subjects, fixation was found at the periphery of the macular hole and more often at its upper edge (13 patients in the triamcinolone acetonide group and 12 patients in the infracyanine green group). In the triamcinolone acetonide group fixation was stable in 9 patients and relatively unstable in the remaining 6 patients. Ten patients in the infracyanine green group had stable fixation and the other 5 patients had relatively unstable fixation. Mean retinal sensitivity in the central 2 degrees was 10.54 ± 3.58 dB in the triamcinolone acetonide group and 9.75 ± 5.04 dB in the infracyanine green group. Mean sensitivity in the central 8 degrees was 13.55 ± 3.22 dB in the triamcinolone acetonide group and 12.36 ± 5.13 dB in the infracyanine green group.
In both groups, retinal sensitivity showed a progressive improvement during the entire follow-up in both the central 8-degree and central 2-degree areas. In the triamcinolone acetonide group the increase was statistically significant at 3 (13.97 ± 4.18, P = .0002), 6 (14.21 ± 3.78, P = .0002), and 12 months (15.05 ± 3.86, P = .0001) after surgery in the foveal area ( Figure 2 ) and at 6 (15.59 ± 3.22, P = .0179) and 12 months (15.89 ± 3.33, P = .005) in the macular area ( Figure 3 ). In the infracyanine green group the increase was statistically significant at 3 (12.77 ± 5.84, P = .0009), 6 (13.89 ± 5.79, P = .0001), and 12 months (14.84 ± 5.82, P = .0001) after surgery in the foveal area and at 6 (14.74 ± 4.93, P = .002) and 12 months (14.99 ± 5.09, P = .0008) in the macular area. No statistically significant differences were observed between groups at any follow-up time point. Fixation stability improved in all patients. At 12 months, 14 patients of each group reached a stable fixation. Two patients (1 in each group) who had a stage 4 macular hole before surgery showed persistence of a relatively unstable fixation.