Klamann, Matthias K.J. MD; Maier, Anna-Karina B. MD; Gonnermann, Johannes MD; Ruokonen, Peter C. MD
Primary open-angle glaucoma (POAG) is a progressive optic neuropathy in which there is loss of retinal ganglion cells and corresponding nerve fiber layer loss, resulting in visual field (VF) defects; it may lead to blindness. Elevated intraocular pressure (IOP) is the major risk factor for the development and progression of glaucoma, and it is the only modifiable risk factor. There are several methods to reduce IOP: medical treatment, laser treatment, and surgery. Selective laser trabeculoplasty (SLT) is performed with a 532-nm Nd:YAG laser, and targets the pigmented cells of the trabecular meshwork without causing thermal or collateral damage to the surrounding structures.1 SLT has been shown to produce IOP lowering similar to argon laser trabeculoplasty.2,3 Various clinical studies have demonstrated the efficacy and safety of SLT in producing a sustained reduction in IOP.1,2,4–10 SLT has also been shown to be effective as both a primary treatment and an adjunct to medical therapy.8–10
Regarding adverse effects after SLT, inflammation in the anterior chamber is described in several papers.11 Ayala et al11 reported no significant difference in anterior chamber inflammation before and after SLT, measured clinically with a slit lamp and objectively with a laser flare meter. Nagger et al10 reported transient ocular discomfort and mild uveitis during the first week after SLT treatment.
Information in the literature regarding panophthalmic inflammation status was very rare (ie, retinal or vitreous behavior after SLT treatment). Only 1 reported case of cystoid macular edema (CME) after SLT is actually published.12
The purpose of the present study was to clinically assess relevant inflammation in the anterior chamber and inflammatory signs in the vitreous and retina after 360 degrees SLT treatment. Second, short-term results after SLT, in addition to nonsufficient local therapy in moderate POAG, were examined.
MATERIALS AND METHODS
Sixty-four eyes of 64 consecutive patients were enrolled into this prospective study, from July 2010 to February 2012. All had moderate POAG that was poorly controlled by medical treatment. Medical treatment before and after SLT is presented in Table 5. According to VF function and cupping of the optic nerve head, in all cases target IOP was determined to be >15 mm Hg. No eye had been previously treated with a laser or filtering surgery. Exclusion criteria are listed in Table 1.
Informed consent for both participation in the study and SLT treatment was obtained from each patient before the treatment. The authors have considered the ethical aspects of the study and followed the guidelines of the Helsinki Declaration.
Each study participant underwent a complete ophthalmological examination, including a medical history review, best-corrected visual acuity measurement, slit-lamp biomicroscopy, intraocular pressure (IOP) measurement using Goldmann applanation tonometry, gonioscopy, dilated fundus examination, stereoscopic photographs of the optic disc, and a baseline bilateral standard automated perimetry threshold VF test using the 24-2 Swedish interactive threshold algorithm (Octopus, Haag-Streit).
Moderate POAG was diagnosed as elevated IOP above determined target pressure of 15 mm Hg by a Goldmann applanation tonometer, glaucomatous cupping on funduscopic examination, and open angle in gonioscopy. The optic disc was examined using the diagnostic criteria described by Jonas,13 depending on the degree of glaucomatous cupping, ranging from 0 to V. Cupping was evaluated by 1 examiner only. Gonioscopy was examined using Shaffer classification. Eyes classified as glaucomatous had 3 consecutive (repeatable) abnormal VF test results (pattern standard deviation outside the 95% confidence limits and/or a glaucoma hemifield test result outside normal limits).
Clinical evaluation of inflammation in the anterior chamber was carried out with a slit lamp. The beam of the slit-lamp microscope projected at 45 degrees transverses the cornea and shows light scattering in the anterior chamber and cellular inflammatory exudates in the aqueous humor. The light intensity and magnification of the slit lamp should be maximal; the beam should be 3 mm long and 1 mm wide.
Grading was performed as proposed by the Standardization of Uveitis Nomenclature (SUN) Working Group.13 Anterior chamber cells were graded on the ordinal scale of 0 (<1 cell/1 mm2, high-intensity beam), 0.5+ (1 to 5 cells/beam), 1+ (6 to 15 cells/beam), 2+ (16 to 25 cells/beam), 3+ (26 to 50 cells/beam), or 4+ (>50 cells/beam). AC flare was graded on the ordinal scale of 0 (none), 1+ (faint), 2+ (moderate; iris and lens details clear), 3+ (marked; iris and lens details hazy), or 4+ (fibrin or plastic aqueous). Vitreous cells were graded as present or absent. Vitreous haze was graded along an ordinal scale of 0, 0.5+, 1+, 2+, 3+, or 4+. Grading of vitreous cells and vitreous haze was made with the pupil dilated.
As inflammatory processes may be inherent to the mechanism of action of SLT, we postulate that upregulation of inflammatory pathways could trigger a CME.
To detect an increment of retinal thickness according to macular edema after SLT treatment, mean retinal thickness was assessed using the Spectralis OCT as described.
All optical coherence tomography (OCT) scans were performed with the Spectralis OCT. The instrument combines OCT technology with a confocal Scanning Laser Ophthalmoscope (Heidelberg Engineering; Heidelberg, Germany), which provides a reference fundus image. Each OCT B-scan will be registered and locked to a reference image.
OCT software can identify previous scan locations and “guide” the OCT laser to scan the same location again. For this purpose, the first complete volume scan was set as a reference scan. The Spectralis OCT has a follow-up function to ensure that the same scanning location is identified on following visits by the tracking program. In addition, eye tracking and the high scanning speed are supposed to reduce moving artifacts. For OCT scanning, the Spectralis OCT provides an Automatic Real-Time (ART) function for increased image quality. With ART activated, multiple frames (B scans) of the same scanning location are performed during the scanning process and images are averaged for noise reduction. The number of frames can be adjusted. In this study, the ART function was turned on and 3 frames were acquired for each B-scan location to reduce noise and to improve image quality. Scans were acquired in the high-resolution acquisition mode. Scans with low quality and a failing retinal thickness algorithm were excluded and measurements were repeated until good quality was achieved. In addition, scans with blinks during the scanning process were excluded and repeated. Retinal thickness values were calculated for 9 areas corresponding to the Early Treatment Diabetic Retinopathy Study (ETDRS) areas. The ETDRS plot consists of 3 concentric rings with diameters of 1, 3, and 6 mm. The 2 outer rings are divided into quadrants by 2 intersecting lines. The ETDRS grid was positioned automatically by the Spectralis OCT software and retinal thickness values were extracted as captured. No manual adjustments of the grid were performed by the operator.
The SLT is a q-switched, frequency-double Nd:YAG, and wavelength of around 532 nm. The SLT uses a single pulse with a pulse duration of 3 ns; the spot size is estimated to be 400 µm. In this study, SLT treatment was performed 360 degrees with the Trabeculas SLT (A.R.C. Laser; Nuernberg, Germany) using 95 to 105 spots applied to the trabecular meshwork. The initial energy used was 0.9 mJ. The energy was increased or decreased until bubble formation appeared, and was then decreased 0.1 mJ for the remainder of the treatment. The energy used in this study was between 0.8 and 1.4 mJ. All patients continued with the same antiglaucomatous medical treatment after SLT. Patients were pretreated with topical 1% pilocarpine 1 hour before SLT. No patient was treated with corticoids or nonsteroidal anti-inflammatory drugs before or after SLT treatment.
The patients were examined before treatment and 24 hours, 14 days, 6 weeks, and 3 months after treatment. The mean of 2 IOP measurements conducted with the Goldmann applanation tonometer was recorded as the final IOP value. If the difference between the 2 IOP measurements exceeded 3 mm Hg, a third measurement was made, and the mean of the 3 measurements was recorded as the final IOP value. Further anterior chamber flare, vitreous haze and cells, and macular thickness were measured in the way prescribed.
SLT treatment was performed by 1 experienced surgeon (P.R.). Grading of inflammation, IOP measurement, and OCT scanning were conducted by another examiner (M.K.) independently.
Normally distributed variables were compared with the independent sample t test. Numeric variables that were not normally distributed were compared with the Mann-Whitney U test. All tests were 2-tailed and a 5% significance level was maintained throughout. The procedures of the analysis program PAWS (v. 18.0, version for Mac) were used. At all times, P values <0.05 were determined to be significant.
Patient demographics are presented in Table 2. All patients were treated with SLT for the first time. As shown in Table 3, eyes treated with SLT showed statistically significant mean IOP reductions from baseline at each time interval (P<0.001).
IOP on baseline and 24 hours, 14 days, 6 weeks, and 3 months post-SLT was 19.1±3.972, 12.9±2.513, 13.2±3.331, 14.1±2.731, and 13.9±2.922 mm Hg, respectively.
Table 4 shows the change in the number of glaucoma medications over time. Overall, the decrease in medications ranged from 15% to 27% 3 months after SLT treatment.
There was no statistically significant increase in mean retinal thickness in any of the 9 ETDRS areas from baseline in follow-up examinations (Table 5). There were no clinically relevant signs of inflammation in the anterior chamber or in the vitreous according to the SUN classification14 at any time of examination. Ten OCT examinations had to be repeated directly because of bad scan quality, failing retinal segmentation algorithm, or blinks during the scanning process. After repeated examinations, all eyes could be included for further analysis.
The present study shows that SLT treatment produces no clinical relevant inflammation when the eyes were treated in 360 degrees. Neither inflammation in the anterior chamber nor in the vitreous and retina were found. In this study, no postoperative medication was used, neither nonsteroidal or corticoids.
Inflammation in the anterior chamber is described in several papers. Some authors reported no significant difference in anterior chamber inflammation before or after SLT measured clinically with slit lamp and objectively with the laser flare meter.11 Measuring anterior chamber cells with the slit lamp, we did not even find clinically significant inflammation at any time during the follow-up examinations compared with the baseline. These findings stand in contrast to some previous studies in which inflammatory reactions to SLT are well recognized. Realini15 reported ciliary injection and anterior chamber inflammation after SLT, whereas Kim and Singh16 published a report about severe iritis and choroidal effusion following SLT. Nevertheless, the lower inflammation found in our study was present, although we performed SLT in 360 degrees of every eye without additional preoperative or postoperative medical treatment.
The initial energy used in our study was 0.9 mJ, which is similar to other studies. Proximately, the energy was increased or decreased until bubble formation appeared, and was then decreased 0.1 mJ for the remainder of the treatment. According to our treatment procedure, there was not a bubble formation with each pulse that is different to other studies. In our cases, about 50% of the pulses had a bubble formation. We assume that bubble formation is important for the effectiveness of the procedure; but too much bubble formation may lead to a higher rate of inflammation.
Information about vitreous inflammation after SLT treatment is very scarce. Regarding vitreous haze and cells after SLT, we did not find inflammatory reactions at any time during follow-up compared with the baseline examination.
The exact pathogenesis of CME remains uncertain. CME develops when excess fluid accumulates within the macular retinae.17 This is thought to occur after disruption of the blood-retinal barrier. CME represents a common pathologic sequel of the retina and occurs in a variety of pathologic conditions such as intraocular inflammation, central or branch retinal vein occlusion, diabetic retinopathy, and following cataract extraction.17 Irvine18 initially reported CME following cataract surgery. As inflammatory processes may be inherent to the mechanism of action of SLT as well, we postulate that upregulation of inflammatory pathways could trigger a CME. However, there is only 1 case report of macular edema after SLT.12 In our study, we did not find a significant increment of retinal thickness measured by OCT in any of the 9 ETDRS areas conducted. Comparing follow-up to baseline examination, no macular edema was denoted at any time.
To the best of our knowledge, this is the first study investigating clinically significant inflammation in the anterior chamber, vitreous, and retina after SLT treatment treating 360 degrees, without any kind of anti-inflammatory treatment before and after SLT. Limitations of this study include the missing of posttreatment IOP spikes acquisition within the first 24 hours. To exclude a potential IOP elevation directly after SLT, the IOP should be closely meshed.
With regard to the IOP-lowering effect of SLT, we found a significant IOP reduction after SLT treatment in addition to nonsufficient local antiglaucomatous therapy. These results correlate well with findings previously published. Ayala et al11 found a mean IOP reduction of about 6.75 mm Hg 1 month after treatment. Latina et al1 presented a mean IOP reduction of about 6 mm Hg 1 month after SLT and 5.8 mm Hg after 26 weeks. Compared with the findings of Song et al19 the IOP lowering in the previous study was higher. The major different between both studies is that SLT was performed in 360 degrees in our study, whereas it was performed in 180 degrees in the study from the Duke University Medical Center. Further the average spot number in the Duke study was 44, whereas it was 99 in our study. As the number of spots is known as a factor of success,19 the higher IOP-lowering effect of our study may be explained. However, the baseline IOP in the present study was relatively low compared with previous studies. Nevertheless, a fairly remarkable IOP lowering was denoted. Mean target pressure could be achieved during 3 months with an additional decrease of antiglaucomatous medications in 82% of the patients. Regarding the significant IOP lowering 24 hours posttreatment, the influence of preoperative pilocarpine should be considered.
In summary, SLT has the potential to effectively lower IOP in eyes with moderate POAG in addition to nonsufficient local therapy. If inflammatory processes are inherent to the mechanism of action of SLT, this may affect the anterior chamber as described in a previous paper, but seems not to affect the vitreous or retina. Further studies need to be conducted to detect inflammatory signs in pseudoexfoliative or pigmentary glaucoma following SLT.
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