Spark Imagewise 68 – Asymmetrical response to mitomycin-C in bleb formation

Dr. Prerna Agrawal, Dr. Sarang Lambat, Dr. Prabhat Nangia, Dr. Vinay Nangia.

Case Description
A male, 45 years of age, presented to us on May 8th, 2022. The best corrected visual acuity was 6/9 in the right eye (RE), and it was 6/6 with +0.50DC @ 30 degrees in the left eye (LE). He was on travoprost 0.004% eye drop HS in Both eyes (BE) and tablet acetazolamide once daily for 1 year. Anterior segment examination showed conjunctival congestion in BE without any other finding. Intraocular pressure in RE was 14 mmHg, and in the LE, it was 15 mmHg with 2 antiglaucoma medications. He had open angles on gonioscopy. Central corneal thickness was 537µ in RE and 528µ in LE. The axial length was 24.61 mm and 24.51 mm in RE and LE, respectively. The vertical cup disc ratio was 0.9 in BE. He was diagnosed as having primary open-angle glaucoma. He has advised brimonidine tartrate 0.2 % and timolol 0.5% in addition to travoprost and tablet acetazolamide. He was also advised low dose steroid eye drop in tapering dose in BE for the conjunctival allergy to the drops.
 Due to intolerance to topical antiglaucoma medication, he underwent a trabeculectomy with MMC on 21st May 2021 in the RE.
Since IOP was elevated at 35 mmHg, he underwent bleb massage followed later by laser suture lysis. The IOP following laser suture lysis was 17 mmHg. He later developed a bleb leak with an IOP of 8 mmHg. On 1st June 2021, he underwent conjunctival resuturing, following which the IOP increased to 13 mmHg. He underwent LE trabeculectomy with MMC on 7th June 2021. In the left eye, also on account of elevated IOP, he underwent bleb massage and laser suture lysis, which helped to reduce the IOP to 2 mmHg. The patient developed choroidal detachment, which gradually resolved with the IOP becoming 10 mmHg.

Fig. 1 Anterior segment photograph of the RE shows a diffuse moderately elevated bleb. (outlined in red dashed lines)
Fig. 2 Anterior segment photograph of the LE showed an avascular thin cystic bleb with medium height (more elevated and localized compared to the RE).(outlined  in red dashed lines)

Fig. 3a Anterior segment optical coherence tomography of the RE (horizontal scan) showed a relatively thick-walled bleb with a clear cavity (red arrow) and some slit-like spaces (yellow arrow). The outer wall thickness was 100 µ (blue arrow).
Fig 3 b Indicates the position of the horizontal scan.

Fig. 4a Anterior segment optical coherence tomography vertical scan of the right eye shows anteroposteriorly oriented cavity (red arrow). Note the absence of a meshwork-like appearance that is normally seen in functional blebs.
Fig 4 b Shows the position of the vertical line scan.

Fig. 5a Anterior segment optical coherence tomography horizontal scan of the left eye showed thin irregular septae with cavitations of different sizes representing the internal bleb architecture (red arrows). The outer wall thickness was 80 µ (white arrow). The scleral flap thickness was 220 µ (green arrow), and the space under a scleral flap was 200 µ (yellow asterisk).

Fig. 5 b Shows the position of the horizontal line scan.

Fig. 6 a Anterior segment optical coherence tomography of the left eye using vertical line scans, showed multiple cystic cavities with a variable meshwork (red arrows)  In addition, there is a subsacral space seen below the superficial scleral flap. ( yellow arrow)
Fig. 6 b Indicates vertical line scan.

Fig. 7 Colour photograph of the fundus of the RE showed a cup disc ratio of 0.9 with generalized rim loss (red arrow). There is a total loss of retinal nerve fiber loss striation in the superior and inferior arcade.

Fig. 8 Colour photograph of the fundus of the LE showed a cup disc ratio of 0.9 with generalized rim loss (red arrow). There is a total loss of retinal nerve fiber loss striation in the superior and inferior arcade.

Fig.9 Right eye OCT circumpapillary retinal nerve fiber layer (RNFL) showed marked thinning in all sectors (Fig.9b, white arrows) (Fig.9d, black).

Fig.10 Left eye OCT circumpapillary retinal nerve fiber layer (RNFL) showed marked thinning in all quadrants (Fig.10b, white arrows) (Fig.10d, black arrows).

Discussion:

Our patient presented with significant cupping and intolerance to glaucoma medications. As a result, he was advised to undergo trabeculectomy in both eyes.  Postoperatively after bleb massage and laser suture lysis, the IOP stabilized and was well controlled in the low teens. This case demonstrates the debate and dilemma over glaucoma surgery in a patient with significant cupping,  with reasonably controlled IOP at 15 mmHg. He underwent surgery because of intolerance to drops. Postoperatively the patient had  IOP that increased, and finally, after using post-op methods of massage and laser suture lysis came down to the required levels. This tells us that we may never be sure of being able to control pressure adequately when we do take up a patient for surgery, given the uncertain response of an individual patient and the individual eye to trabeculectomy. 
We used Mitomycin-C in both subjects under the conjunctiva at a concentration of 0.4 mg/ml and for 3 minutes. It is apparent that even using the same technique, there may be sufficient variables in the release of mitomycin-C, the response to mitomycin-C of the individual eye, and the healing response of the conjunctiva. The appearance of the bleb in the two eyes is very different. One may have assumed that given it is the same patient on the same medication for the same duration, and the response would be similar if not identical. However, the bleb appearance is different even clinically (Fig. 1 and 2). Anterior segment OCT image of the RE shows (Fig 3a and 4a) shows a thick-walled conjunctiva (yellow) along with a large cavity (Fig 3a and 4a, red arrows) that runs both horizontally and vertically. The bleb of the left eye (Fig 5a and 6a, red arrows) has irregular spaces separated by thin septae. The difference in the appearance of the two blebs is significant, even though both the conjunctiva were exposed to the exact duration of MMC exposure and underwent the same surgical procedure by the same surgeon. Both the blebs, however, are functioning well and have helped reduce the IOP in the RE to 13 mmHg and in the LE to 10 mmHg.
The bleb of the left eye (Fig 5 and 6), though, gives us cause to worry. As glaucoma surgeons, even as we appreciate the significant reduction of IOP, we may fear that the bleb in the left eye has a fragile outer wall of 80 µ (Fig 5a, white arrow) compared to the RE with an outer wall thickness of 100 µ (Fig 3a, blue arrow). This means that the left eye would be more susceptible to developing a breakdown of the outer wall leading to a bleb leak, increasing the possibility of bleb infection and endophthalmitis. They are also more predisposed because the conjunctiva, exposed to MMC, is now avascular and, therefore, cannot protect itself. These patients are often prescribed long-term topical antibiotics to protect them from developing bleb infections and endophthalmitis.

Read Wise

  1. Khamar MB, Soni SR, Mehta SV, Srivastava S, Vasavada VA. Morphology of functioning trabeculectomy blebs using anterior segment optical coherence tomography. Indian J Ophthalmol. 2014 Jun;62(6):711-4. doi: 10.4103/0301-4738.136227. PMID: 25005200; PMCID: PMC4131325.
  2. Hamanaka T, Omata T, Sekimoto S, Sugiyama T, Fujikoshi Y. Bleb analysis by using anterior segment optical coherence tomography in two different methods of trabeculectomy. Investigative Ophthalmology & Visual Science. 2013 Oct 1;54(10):6536-41.

QuizWise

Q.1 Which of the following classification systems is used for grading the bleb and score for bleb?
A) Indiana Bleb Appearance Grading Scale
B) Moorfields Bleb Grading System
C) Wuerzburg bleb classification system

D) All of the above

Q.2 Mitomycin C is isolated from which of the following?
A) Recombinant DNA
B) Streptomyces caespitosus
C) Papaver somniferum
D) All of the above

Q.3 Which of the following are the side effects of mitomycin C?
A) Bleb leakage
B) Endophthalmitis  
C) Cystic bleb
D) All of the above  

Q.4 Where is mitomycin-C used in ophthalmology besides trabeculectomy?
A) Pterygium surgery
B) Conjunctival neoplasia
C) Cicatricial eye disease
D) All of the above

Correspondence

Dr Vinay Nangia
MS, FRCS, FRCOphth
Director 
Suraj Eye Institute
Email – education@surajeye.org
 

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