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Mitomycin-augmented non-penetrating deep sclerectomy: preoperative gonioscopy and postoperative perimetric, tonometric and medication trends
  1. William Eric Sponsel1,
  2. Sylvia Linner Groth2
  1. 1Biomedical Engineering, University of Texas, WESMDPA Glaucoma Service, San Antonio, Texas, USA
  2. 2University of Minnesota Medical School, Minneapolis, Minnesota, USA
  1. Correspondence to Professor William Eric Sponsel, Suite 306 Madison Square Building, 311 Camden Street, San Antonio, TX 78215, USA; sponsel{at}earthlink.net

Abstract

Background/Aims Non-penetrating deep sclerectomy (NPDS) can enhance drainage of aqueous humour without disrupting the trabecular endothelial layer, reducing risks of postoperative hypotony and hyphema. This study explores associations of angle morphology with surgical efficacy in eyes with open and obstructed angles.

Methods Eighty-nine consecutive eyes undergoing successful NPDS (non-implant, with 0.4 mg/ml mitomycin C and limbus-based two-layer closure) were studied in this institutional review board-approved retrospective quality assurance study. Postoperative complication frequency, intraocular pressure (IOP), glaucoma medications required and acuity were monitored (baseline vs 3, 6, 9, 12 and 18-month postoperative levels), along with 30-2 Humphrey MD and corrected pattern standard deviation (CPSD) (baseline vs 6, 12 and 18-month postoperative values). Preoperative gonioscopy was compared with the subsequent requirement for specific postoperative interventions.

Results IOP at all five postoperative intervals was reduced (22±0.9 to 12±0.5 mm Hg; p<0.0001). No hyphema were observed. Postoperative hypotony (IOP < 4 mm Hg) occurred rarely (8/445; 1.8%). Mean glaucoma medication use dropped from 3.1±0.1 to 0.23±0.1 at 18 months (p<0.0001). Mean 30-2 MD improved by approximately 1.4 dB at 6, 12 and 18 months (p<0.002); CPSD remained stable.

Conclusions Following NPDS, a sustained IOP decrease of 10 mm  Hg (45%) was attained, with stable acuity, increased perimetric generalised light sensitivity and 90% reduction in medical therapy requirement. Morbidity risk was associated with narrow gonioscopic angle insertion and synechia, but not with shallow approach or trabecular pigmentation.

  • Clinical Trial
  • Treatment Surgery
  • Field of vision
  • Glaucoma
  • Intraocular pressure

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Introduction

Non-penetrating deep sclerectomy (NPDS) is a glaucoma filtering procedure designed to control intraocular pressure (IOP) by enhancing the drainage of aqueous humour without disrupting the trabecular endothelial layer. NPDS1–3 is a modification of standard trabeculectomy,4 ,5 the established primary surgical procedure for most medically refractory glaucoma. Because the anterior chamber is not breached, hyphema and hypotony maculopathy are uncommon after successful NPDS.6 ,7 For this reason, patients for whom such complications are of predictable concern, including those with a history of uveitis or maculopathy, may be referred specifically for NPDS. This can present various other inherent challenges. As NPDS incorporates no peripheral iridectomy, eyes with shallow angles may be prone to iris incarceration, and post-uveitic eyes to pigmentary trabecular obstruction. The purpose of this study was to relate preoperative gonioscopy to postoperative morbidity, and document NPDS surgical efficacy in terms of IOP, medication requirement and visual field status during an 18-month follow-up period among eyes with a spectrum of open and obstructed angles.

Methods

This institutional review board-approved study includes all eyes of all patients undergoing NPDS with mitomycin C between January 2008 and June 2010, excluding those converted to full-thickness trabeculectomy at the time of surgery for any reason. Clinical assessments were made preoperatively and at 3 months (±2 weeks), 6 months (±1 month), 9 months (±6 weeks), 1 year (±2 months) and 2 years (±3 months) postoperatively. In each instance only data from the single visit nearest to the assigned time interval was used.

All eyes were submitted to Zeiss four-mirror gonioscopy preoperatively using the Spaeth grading system8 documenting: (1) the level of apparent iris insertion (A (angle obscured) to E (extensive ciliary body)), with and without goniocompression; (2) the approach of the peripheral iris to the cornea (0–50°); (3) the shape of the peripheral iris (q, concave; r, flat; s, steep); and (4) the degree of iris pigmentation (0–4).

Medications, tonometry, refraction and best-corrected visual acuity were documented preoperatively and 3, 6, 9, 12 and 18 months postoperatively, by certified ophthalmic technicians naive to the study. Best-corrected acuities were measured scotopically (Acuity System 3.8; Temecula, California, USA; converted to integer function), and IOP by Goldmann applanation tonometry.

Humphrey II visual field (HVF) 30-2 size III stimulus SITA full threshold static perimetry was performed (with best-corrected near refraction) preoperatively, and 6 (±1.5), 12 (±3) and 18 (±4.5) months postoperatively, on all capable subjects with acuity greater than 20/80. Fields yielding false-positive, false-negative, or fixation loss rates greater than 33% were excluded. Antiglaucoma medications (topical and oral) were documented at each visit, combination agents counting as two drugs.

All surgeries were performed on consenting adult patients after thorough discussion of the risks and potential benefits of NPDS. The principal steps of the procedure used are illustrated in figure 1. A 4-0 silk stay suture was placed, with posterior conjunctival incision and anteriorly offset tenons incision. Episclera was debrided using blunt dissection, and 27-gauge electrocautery applied for haemostasis. A 6×6 mm superficial scleral flap of 30% depth was scribed (figures 1A, B) using a ruby crescent blade. A diamond knife was then used to outline the internal sclerostomy to a scleral depth of 90%, dissected with the ruby blade anteriorly over Descemet's membrane (figure 1C). The deep scleral flap was carefully excised (figure 1D), using the diamond blade. Schlemm's canal was unroofed using Mermoud microforceps (figure 1E). Cellulose sponges containing 0.3 ml of 0.4 mg/ml mitomycin C were applied, one to the scleral bed and two between the closed external scleral flap and tenons capsule, each for 1 min, followed by saline irrigation. No scleral implants were placed.9–11 The scleral flap was repositioned using three 10-0 nylon sutures (figure 1F). Tenons capsule and conjunctiva were closed separately using continuous 8-0 polyglactin on tapered needle, locking in the tenons layer and non-locking in the conjunctiva (figure 1G), leaving a spontaneously elevated bleb (figure 1H). Antibiotic/steroid ointment was applied, and patch and shield were placed. Topical moxifloxacin 0.5% (Vigamox; Alcon, Fort Worth, Texas, USA) and prednisolone acetate 1.0% (Omnipred; Alcon) were tapered for 1 month postoperatively. Patients were seen 1, 7 and 21 days postoperatively, and at the study intervals noted above.

Figure 1

Modified Mermoud10 non-penetrating deep sclerectomy: After placement of superior rectus stay suture and formation of limbus-based conjunctival flap, margins for a one-third thickness external scleral flap are scribed using a 4.1518 NPGS diamond step knife (Huco Vision SA, St Blaise, Switzerland; http://www.hucovision.com) and the flap is elevated using the Huco 4.1495 Mermoud ruby crescent blade (A). The dissection is carried into the corneal descemeto-scleral junction (B). After scribing the internal scleral lake margin 1 mm from the external flap bed margin using the 4.500 Mermoud 25° diamond NPGS diamond knife, the internal flap is elevated using the 4.1494 Sourdille crystal sclerokeratectomy knife (C) and removed with 4.2350 Galand corneal scissors (D). After identifying and liberating the edge of the external trabeculum with the Mermoud diamond knife, it is peeled away using the 3.4475 Mermoud NPGS forceps (E). After applications of mitomycin C (see text) the external flap is reaffixed with three 10-0 nylon sutures across its posterior margin (F). The tenons capsule is closed with running 8-0 polyglycan locking suture, followed by the conjunctiva with tightly spaced non-locking bites in the reverse direction using the same suture on a BV tapered needle (G). The new bleb elevates spontaneously as the suturing is completed (H). This figure is only reproduced in colour in the online version.

Any occurrences of postoperative hypotony (IOP < 4 mm Hg), hyphema or bleb leak were documented, as were all clinical or surgical corrective manoeuvres performed during the 18-month follow-up (eg, anterior chamber reformation, laser procedures, needling bleb re-elevation). Specific indications were as follows: Reformations with 0.9% NaCl solution were performed at slit lamp whenever angle shallowing threatened to obstruct aqueous outflow, and/or instances of hypotony (IOP < 4mm Hg). Focal argon iridoplasty was performed (300 micron spot, 460 mW, 0.5 s) superiorly if the pupil was peaked or iris root incarcerated into the NPDS drainage zone. YAG goniopuncture was performed whenever IOP exceeded 18 mm Hg, using multiple 9.6–11.4 mJ impacts to trabeculum and Descemet's via Zeiss four-mirror lens. Focal iridectomy was performed bimanually via paracenteses using retinal forceps and microscissors in instances of irreducible iris incarceration into the drainage zone. Re-elevation of flattened blebs was performed with a bent 25-gauge needle.

Statistical analysis of each of the variable sets (IOP, medications, acuity, Humphrey MD and corrected pattern standard deviation; CPSD) confirmed that each dataset had a normal distribution with properties of an equal interval scale (CPSD and MD are linear expressions exponential light attenuation). Each sample included all available data for each variable from the source population. Differences from baseline for each variable were compared at each time interval postoperatively using Student's paired t test. Analyses of trends in MD and CPSD were carried out for all eyes with qualifying Humphrey 30-2 SITA full threshold fields 4–8 months preoperatively, comparing the single fields nearest 6, 12 and 18 months postoperatively versus baseline.

Results

Of 100 eyes in which NPDS dissections were initiated during the study interval, 11 were converted to full-thickness trabeculectomies and are thus excluded from this analysis. The remaining 89 consecutive eyes of 67 patients who underwent NPDS with mitomycin C during the 18-month study initiation period are all included (61 women, 28 men). Thirty-nine of the eyes (44%) had primary open angle glaucoma, 40 eyes (45%) had some form of chronic angle closure glaucoma, and 10 eyes (11%) had a uveitic history with dense pigmentary obstruction of the trabecular meshwork. Patients’ mean age at the time of surgery was 69.1±(SEM) 1.7 years. Thirty-three patients were of Hispanic ethnicity, 29 Caucasian and African American. Relevant data are summarised in figures 25.

Figure 2

Sustained mean intraocular pressure (IOP) reduction among patients undergoing non-penetrating deep sclerectomy with mitomycin C. Error bars show the SE of the mean; p value for IOP change relative to preoperative level for all postoperative time intervals <0.0001.

Figure 3

Sustained mean medication reduction among patients undergoing non-penetrating deep sclerectomy with mitomycin C. Error bars show the SE of the mean; p value for IOP change relative to preoperative level for all postoperative time intervals <0.0001.

Figure 4

Preoperative baseline Humphrey mean deviation (MD) versus 18 months postoperative Humphrey MD. Note the intra-individual correlation of the perimetric data, and that 88% of eyes were stable or improved at 18 months (ie, on or above the x=y diagonal axis).

Figure 5

Preoperative baseline Humphrey corrected pattern standard deviation (CPSD) versus 18 months postoperative Humphrey CPSD. Note the intra-individual correlation of the perimetric data, and the overall stability of CPSD (x=y diagonal axis).

IOP reduction without tachyphylaxis was noted at all five postoperative intervals, from preoperative 22.1±0.9 mm Hg to 12.1±0.5 at 3 months, 12.3±0.5 at 6 months, 12.1±0.5 at 9 months, 12.3±0.4 at 12 months and 12.1±0.5 at 18 months (Δ-10 mm Hg; 45% reduction; p<0.0001; figure 2). Mean glaucoma medication use dropped from 3.1±0.1 to 0.28±0.1 at 3 months, 0.32±0.1 at 6 months, 0.39±0.1 at 9 months, 0.35±0.1 at 12 months and 0.38±0.1 at 18 months (−87% to −91%; all p<0.0001; figure 3).

Qualifying Humphrey II VFA 30-2 size III stimulus SITA full threshold visual fields were available for over two-thirds (61/89; 69%) of eyes, with a mean of more than four fields before the baseline visual field in the clinical record for the 61 qualifying eyes.12 Additional visual fields were alluded to in written referral correspondence from referring practitioners. There was thus a high degree of previous perimetric experience among the study participants,12 ,13 thereby abrogating learning effect as a likely confounding factor. Among eyes for which qualifying sets of Humphrey II VFA 30-2 size III stimulus SITA full threshold fields were available 4–8 months preoperatively (n=29), both MD and CPSD had deteriorated significantly (MD by −1.82 dB; p=0.004 and CPSD by 0.89 dB; p=0.015), so regression to the mean might complement any physiological effect.

Following NPDS, Humphrey 30-2 MD showed sustained improvement, from a mean preoperative baseline level of −11.76±(SEM) 0.95 dB to −10.27±1.0 at 6 months (n=51; p=0.0016), to −10.46±0.9 dB at 12 months (n=61; p=0.0002) and −10.33±1.1 dB at 18 months (n=51; p=0.0002). CPSD remained statistically unchanged from its preoperative mean value at 6, 12 and 18 months. There was very high intra-individual reproducibility for both global indices at each interval, with correlation coefficients for all 12 comparisons of MD and CPSD clustered around R=0.9 (range 0.863–0.957; all p<0.0001), demonstrating remarkable consistency of intra-individual perimetric performance across the 253 visual fields analysed for MD and CPSD. Figures 4 and 5 show baseline versus 18-month scattergram linear correlations for MD and CPSD, respectively, showing these associations, and illustrating the relative improvement of MD and stability of CPSD.

IOP was reduced postoperatively in 93% of eyes. MD for 88% of eyes was stable or improved at 1 year. There was thus an inevitably very strong concordance of IOP reduction with generalised visual field improvement. This preponderant association displayed no significant direct or inverse correlation, linear or otherwise, in analyses of MD change versus preoperative IOP, postoperative IOP, IOP change, or percentage IOP change, at any of the three time intervals assessed.

All eyes underwent preoperative Zeiss four-mirror gonioscopy. Fourteen eyes (16%) goniocompressed to a wider apparent angle insertion configuration (three plateaus from A to D, and 11 standard narrow angles, three from A to D, five from A to C, one from A to B, two from B to C and two from D to E). For the purposes of this analysis, the ambient (non-goniocompressed) apparent insertion was considered the reference status, because trabecular obstruction would be most likely with the iris root in its nearest proximity.

Goniopuncture14 and iridectomy were the two most commonly required postoperative manoeuvres (n=19; 21% and n=10; 11%, respectively). The need for Nd:YAG-laser goniopuncture to increase trabecular outflow appeared to be unaffected by trabecular pigmentation, with approximately equal numbers required among each of the five pigmentation categories 0–4. Fourteen of the 19 eyes undergoing goniopuncture (74%) had D configuration angles, 17 (89%) of which had an angle approach of 30–40°. Conversely, half of the eyes (five) requiring iridectomy had A angle insertions, with randomly assorted iris approach values, including at least one iridectomised eye for every 5° iris angle interval between 10° and 45°.

Fifteen eyes required some form of non-laser post-NPDS surgical manoeuvre, nine (60%) arising among the 39 eyes with peripheral anterior synechiae (PAS), yielding a frequency for eyes with preoperative PAS requiring eventual corrective surgery post-NPDS of 23%. Nine eyes (10%) became hypotonous at least once, all among the 10 eyes (11%) requiring postoperative anterior reformation via paracentesis. There were no hyphemata or bleb leaks documented during the follow-up period. Among the 39 eyes (44%) with PAS, 19 (49%) required some form of postoperative manoeuvre in an attempt to maintain efficient filtration.

The six remaining eyes requiring additional incisional surgery (from among the 50 without PAS) occurred at a frequency of 12% (ie, six of 50), approximately half the PAS-associated rate. All six underwent secondary peripheral iridectomy to re-open an iris-incarcerated filtering site, several in combination with a needling revision leaving the internal trabeculum intact. Note that this rate of iridectomy is comparable to that seen among the PAS eyes (ie, four of 39; 10%). Five other non-PAS eyes underwent YAG goniopuncture14 to improve aqueous flow through a pigment-silted internal trabeculum; three required intracameral acetylcholine injection to facilitate miosis-assisted retraction of incarcerated iris root. Only one eye, after secondary iridectomy failed, required trabeculectomy at a different site.

Discussion

These findings should be compared with others,15–21 particularly those of a recent landmark study of mitomycin C-augmented NPDS in eyes with various forms of open angle glaucoma.21 The utility of mitomycin C in NPDS has been reaffirmed in recent placebo controlled case–control analyses.18 Mitomycin C application has long been a standard feature of glaucoma filtration surgery for patients in south Texas. Among this population of glaucomatous eyes of mixed aetiology, a highly significant (45%) mean reduction in IOP was sustained throughout the 18-month follow-up period with appropriate postoperative management. This substantial and stable IOP reduction was accompanied by a 90% reduction in reliance on medical therapy, and a highly significant improvement in generalised light sensitivity (Humphrey 30-2 MD). This global visual field improvement could not be attributed to learning effect, because these patients were already perimetrically experienced. Regression to the perimetric mean or relief from pharmaceutical side effects might have been contributory. Focal visual field loss (CPSD), typically associated with established scotomata, remained constant.

Preoperative gonioscopy showed important associations with postoperative management challenges. Maintenance problems arose in eyes with both narrow and open angles. The methods chosen to mitigate these problems tended to reflect existing gonio-anatomical constraints. Goniopuncture was frequent in eyes with preoperatively wide-open angles, presumably because of easy laser access to the trabeculo-Descemet's window, and a lower risk of iris incarceration once aqueous flow was restored. Iridectomy was frequent among eyes with imminent or actual iris incarceration into the NPDS drainage zone, typically associated with either PAS or A-insertions on preoperative gonioscopy. The absence of an association between iris approach angle and the development of outflow obstruction requiring laser or surgical remediation is surprising, suggesting that the proximal angle character contributes a greater risk of iris incarceration after NPDS than midperipheral iris bowing. Another counterintuitive finding was that trabecular pigmentation was not predictive of the eventual need for iridectomy or goniopuncture after NPDS. This suggests that the surgically isolated inner trabeculum may be spontaneously cleared of debris and freely transmit aqueous after NPDS, regardless of the extent of trabecular pigmentation preoperatively. If reaffirmed, this would extend the range of straightforward candidates for NPDS to include eyes with stabilised post-uveitic open angle glaucoma.

Nearly half the eyes among this heterogenous glaucoma referral population required some form of postoperative maintenance procedure, many with preoperatively wide-open angles. One in six (17%) eyes required additional corrective incisional surgery that was generally effective in maintaining therapeutic IOP without subsequent morbidity. It is probable that without timely intervention many outcomes might not have been so favourable. Follow-up clinical evaluation of all eyes undergoing mitomycin-augmented NPDS should thus be scheduled at sufficient frequency to identify problems and perform definitive corrective manoeuvres promptly and efficiently.

The purpose of this study was to evaluate eyes of diverse glaucomatous aetiology undergoing successful NPDS, in which Descemet's membrane was unbreached and no primary iridectomy was performed. Penetration of the internal trabeculum can occur on any eye for a variety of reasons, the outcome of which becomes a modified full-thickness trabeculectomy. During the time frame of this study 11 eyes (not included in this analysis) were converted to full-thickness filters with primary iridectomy. All those eyes fared satisfactorily postoperatively, but with some postoperative management issues typical for mitomycin-augmented trabeculectomy, including several instances of hyphema and transient hypotony.

These exploratory findings are encouraging, and provide a sound basis for future prospective randomised studies to explore further the relative utility of NPDS and its apparent efficacy in conserving or even improving visual function. While mastering the technique it is initially advisable to avoid NPDS in eyes with primary and secondary angle narrowing or with anatomical obstruction of the trabeculum.22 ,23 The present study indicates that, with appropriate follow-up and maintenance measures, many such eyes may be cautiously and appropriately submitted to NPDS with positive expectations. As a whole, this mixed population of eyes with open and obstructed angles did not generate postoperative problems at a rate any higher than might be expected with a more typical open angle population.21 Higher postoperative maintenance requirement arising among eyes with synechiae or a more anterior iris insertion on preoperative gonioscopy reaffirms their more challenging character. As long as these impediments are recognised and respected, these significantly positive ocular hypotensive and visual functional outcomes suggest NPDS may have a wide potential range of useful application.

References

Footnotes

  • Contributors Both authors have fulfilled all criteria for byline authorship according to the guidelines of the International Committee of Medical Journal Editors (ICMJE). Both authors performed data analysis, manuscript preparation, manuscript revision, collated relevant references, approved final version to be published and collaborated fully in the preparation of this work. The surgery, data acquisition and clinical assessments were performed by the corresponding author, WES.

    This study was presented in part at the annual meetings of the American Society of Cataract and Refractive Surgery, Chicago, IL, 21 April 2012, the Association for Research in Vision and Ophthalmology, Fort Lauderdale, Florida, 9 May 2012 and the International Congress on Glaucoma Surgery, Glasgow, Scotland, 14 September 2012. This research was commissioned by Right To Sight International.

  • Competing interests William Eric Sponsel MBChB, MD, FRANZCO is a Primary Investigator with the Australian Research Council Centre of Excellence in Vision Science (ACEVS).

  • Ethics approval This study received ethics approval from the Baptist Medical Center Institutional Review Board.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data sharing statement The Excel spreadsheet containing all the data from which this report is compiled is available and will be emailed upon request.