A 64-year-old white male with a history of open angle glaucoma and trabeculectomy presented complaining of decreasing vision in his left eye. Medical history indicated high cholesterol for which he was taking Zocor (simvastatin). Two years earlier he had trabeculectomy with mitomycin-C via a limbal-based incision, followed a few months later by cataract extraction in his left eye by a glaucoma specialist in California.

The patient was currently taking Xalatan (latanoprost) at bedtime and Trusopt (dorzolamide) tid in his right eye only. He had no known drug allergies.

Diagnostic Data
External ocular examination revealed a slightly enlarged, sluggish reacting left pupil secondary to cataract extraction. Refraction was +0.75-1.50x15 with a BVA of 20/30- O.D. and +0.25-1.00x175 with BVA of 20/40+ PHNI O.S.

Amsler grid testing revealed positive metamorphopsia in the left eye throughout. Intraocular pressures were 18mm Hg O.D. and 4mm Hg O.S. A large filtering bleb with an open scleral flap was present in the superior nasal bulbar conjunctiva of the left eye. A grade 1 nuclear sclerosis was evident in the right eye, while a posterior chamber intraocular lens was present in the left eye. A few corneal sutures were still present in the temporal peripheral cornea of the left eye with a negative Seidel’s sign (figures 1 and 2).

Gonioscopy revealed a 4+ open angle with few iris processes in the right eye, and a grade 1 narrowed angle in the inferior and nasal angles, with a closed temporal angle in the left eye. A sector iridectomy was present in the left superior angle. Indentation gonioscopy made the scleral spur visible in the inferior and temporal angles.

Dilated fundus examination revealed a cup-to-disc ratio of 0.6/0.7 and 0.3/0.3 in the right and left eyes, respectively, with no signs of atrophy or disc engorgement. Binocular indirect ophthalmoscopy indicated a healthy peripheral retina and posterior pole in the right eye. In the left eye however, choroidal wrinkling was present throughout the macula due to chronic overfiltration by the bleb.

Diagnosis
I diagnosed chronic hypotony maculopathy secondary to an open scleral flap within the filtering bleb.

Treatment and Follow-up
Because of the inherent difficulty of resuturing the scleral flap, our glaucoma specialist initially recommended treatment via autologous blood injection into the overfiltering bleb. The patient delayed returning to our clinic for the blood injection, but finally returned six months later. Refraction at this visit was +0.50-1.50x10 with BVA of 20/30+ O.D. and +1.50-1.25x180 with BVA of 20/50- PHNI O.S.

Applanation tonometry measured IOPs of 19mm Hg O.D. and 2mm Hg O.S. B-scan ultrasound of the left eye illustrated a slightly thickened retina (figure 3). Indirect ophthalmoscopy revealed a significantly wrinkled posterior pole with tortuous retinal vessels in the left eye, extending through the macular area. The macular hypotony had worsened, as indicated by the drop in acuity and +1.25D increase in hyperopia. I ordered retinal photographs (figure 4) and rescheduled the patient to see our glaucoma specialist.

The patient was reluctant to have the autologous blood injection. He went to another glaucoma specialist who recommended against any additional surgical or autologous blood treatment. This doctor prescribed Cosopt (dorzolamide-timolol) bid in addition to Xalatan in the right eye only. The patient finally returned to our clinic nine months later for re-evaluation.

At this visit, refraction was +5.75-2.75x150 with BVA of 20/200 PHNI O.S. The dilated exam revealed many vitreous floaters and a hazy fundus view with significant wrinkling of the posterior pole and macular area in the left eye. IOPs were 19mm Hg and 2mm Hg in the right and left eyes, respectively. A new B-scan displayed slightly thickened retina with few vitreous floaters and no evidence of retinal or choroidal detachments.

The patient seemed skeptical about autologous blood treatment, but I warned him of greater risks involved with a second trabeculectomy. I also warned him of the potential for more serious consequences, such as retinal or choroid-al detachments, if he failed to get treatment.

I obtained visual fields (the patient had previously failed to show for previous visual field appointments). Fields revealed inferior nasal arcuate defects in the right eye. The left eye displayed a very depressed overall field with dense superior and inferior nasal field defects (figure 5).

Despite several recall efforts, the patient did not return until, again, nine months later. Acuities at this visit were 20/30 O.D. and 1/400 PHNI O.S. IOPs were 15mm Hg O.D. and 2mm Hg O.S. Anterior chambers were deep and quiet.

The bleb now extended from 8 to 3 o’clock. I could not clearly view the posterior pole of the left eye on dilated examination due to significantly cloudy vitreous opacities and hazy posterior lens capsule. B-scan in the left eye revealed no retinal or choroidal detachments. Only scattered vitreous debris were present.

At this point, our glaucoma specialist recommended the patient have a YAG posterior capsulotomy so we could better view the retina and then schedule surgery for a scleral patch graft. After consultation with another glaucoma specialist, the patient decided against having more surgery on his left eye. He was concerned about controlling the glaucoma in his right eye and elected to follow up with a private glaucoma specialist.

Discussion
Antimetabolites used with trabeculectomy have greatly reduced the risk of filtration failure. However, chronic hypotony, late bleb leaks and endophthalmitis are more common with the use of anti-metabolites (see “Antimetabolite Pharmacology,” page 84).

There are two types of filtration procedures: guarded trabeculectomy, in which the surgeon sutures a scleral flap over the sclerostomy site; and a full-thickness procedure, such as trephination, thermal sclerostomy, or posterior lip sclerectomy, in which the surgeon completely excises the sclera on the area of the sclerostomy.

Guarded trabeculectomy has become the surgery of choice because it has a lower risk of flat anterior chambers, and generally results in less hypotony and cataract formation than the full-thickness procedure. The incidence of hypotony maculopathy is believed to be around 3-5% of all filtering operations. ¹

Successful filtering surgery would create a blister-like elevation of the conjunctiva over the sclerostomy. Bleb appearance varies. In an early postoperative bleb, the adjacent conjunctiva and subconjunctival tissues may be edematous and hyperemic. Weeks later the conjunctiva over the scleral flap will show greatest elevation with much less hyperemia.

Many factors affect the gross morphology and function of blebs. Previous scarring and other stimuli may increase wound-healing response. Corticosteroids and antifibrinolytic agents inhibit the inflammatory and healing response, producing thinner, more cystic blebs.

Thin, cystic, avascular blebs more commonly manifest after trabeculectomy with antifibrosis therapy.² Antiglaucoma drops may also increase inflammatory cell production, cause epithelial metaplasia and reduce goblet cell formation.^3,4

Biomicroscopy should assess anterior chamber depth, and bleb size and shape. Leaking blebs appear flat with a positive Seidel’s sign. An excessively filtering bleb (without leakage), such as that found in this patient, appear elevated.

After filtering surgery, hypotony occurs when IOP falls below 6mm Hg,⁷ perhaps due to decreased aqueous production or excessive aqueous outflow. Persistent hypotony caused by excessive filtration more commonly occurs after full-thickness procedures and the use of antifibrotic agents.⁸

Chronic hypotony that persists for more than three months can result in hypotony maculopathy. Signs include decreased acuity, choroidal folds and retinal striae,⁹ exudative retinal detachment, macular edema, disc edema, phthisis, astigmatism and shallow anterior chamber.¹⁰

Other complications associated with filtering blebs include:

• Bleb leakage. This can occur days or months after surgery. Spontaneous late bleb leaks are more common with avascular thin blebs, and occur more frequently when antimetabolites are used or after full-thickness procedures. Early bleb leaks may occur after trabeculectomies with antimetabolite use.¹¹
• Encapsulated blebs. Also known as Tenon’s cysts, these blebs can develop 2-4 weeks post-op. They appear as localized, high, elevated blebs with vascular engorgement of the underlying conjunctiva and thick connective tissue. Raised IOP after initial lower IOP is a functional characteristic. Long-term IOP control is fairly good, but often requires antiglaucoma drops.
• Bleb failure. This results when obstructed outflow causes IOP to increase. It is important to know the time of onset of increased pressure and the site of aqueous obstruction to properly evaluate.
• Bleb infection. Infection can spread from the subconjunctival space to the anterior chamber, posterior chamber and vitreous. Because the fluid within the bleb is continuous with the anterior chamber, treat any bleb infection as an endophthalmitis.

  Blebitis refers to inflammation limited to the anterior structures, which can spread rapidly to the posterior segment.

Other factors that may increase the risk of infection after filtration surgery include trauma, contact lens wear, infectious conjunctivitis or blepharitis, diabetes, malnutrition or immune system deficiencies.

Bacteria most responsible for bleb-related endophthalmitis usually arise from the normal flora. They include Streptococcus, Haemophilus influenzae or Staphylococcus.¹²

Management Options
Overfiltration is fairly common in the early post-op period, and often resolves spontaneously. It is important that you know how to differentiate between this and bleb leak. The latter typically requires immediate treatment.

Most cases of hypotony with a formed anterior chamber and elevated blebs resolve with routine treatment. Have the patient restrict activities to avoid Valsalva conditions—especially aphakes, post-vitrectomy patients or those with very high pre-op IOP. They are at risk for suprachoroidal hemorrhage.

Treatment is necessary when the anterior chamber is significantly shallow or when large choroidal effusions exist. In the early post-op period, pressure patching can apply direct force to the filtration site, allowing for gradual deepening of the anterior chamber.

Aggressive cycloplegia with 1% atropine or 0.25% scopolamine may further deepen the anterior chamber.¹² Surgery is indicated when more conservative methods are not effective. A flat anterior chamber with lens-cornea touch requires immediate anterior chamber reformation. Left untreated, rapid cataract formation and permanent corneal endothelial damage can occur. Large choroidal effusions require surgical drainage.

The autologous blood injection we considered for this patient is a controversial approach. It has been used after spinal taps to stop persistent spinal fluid and pulmonary air leaks. In the eye, one hypothesis holds that whole blood with fibrin and red cells maximize obstruction of aqueous outflow through the bleb, thus reducing filtration and raising IOP.

Autologous blood also provides cells capable of fibrovascular proliferation, which mitomycin-C (MMC) and 5-fluorouracil (5FU) deactivate. Although these are potent antifibrotic agents, they do not inhibit fibroblast migration.

The literature reports a transient IOP spike immediately after autologous blood injection with no associated visual field deterioration.¹⁴ With successful autologous blood injection, blebs will appear smaller and thicker with time.

The most common complication associated with autologous blood injection is hyphema, preventable with an injection of viscoelastic into the anterior chamber prior to the blood injection. Other complications of this procedure are endophthalmitis, bleb failure, corneal blood staining, corneal graft rejection, increased IOP requiring surgical treatment, vitreous hemorrhage and reactivation of ocular toxoplasmosis.¹⁵

The controversy surrounding autologous blood treatment concerns its effectiveness when surgeons use it prior to attempting scleral patch grafting.¹⁰

Autologous blood injection does not take effect in all cases. Multiple injections may be required to achieve success. Due to the limited success of autologous blood and its associated risks of complications, many surgeons prefer to go directly to scleral patch graft operations.

Follow-up of patients with hypotony varies depending on the etiology of the overfiltration. Follow patients with chronic hypotony at regular intervals until the condition resolves.

Other treatments for patients with persistent hypotony due to excessive filtration are:

• Cryotherapy.
• Thermal coagulation.
• Scleral flap revision.
• Scleral patch grafting.
• Pars plana vitrectomy.
• Palmberg (compressive) sutures.¹⁶

Most glaucoma patients will gain improved IOP control after filtering surgery.

However, guarded filtration procedures with use of antimetabolites are associated with an increased risk of hypotony maculopathy. Autologous blood injection or surgical revision of the filtration site can treat hypotony maculopathy successfully. Doctors must follow these patients closely because they can develop retinal or choroidal detachments. The sooner one initiates intervention, the better the prognosis for restoration of vision.

Dr. Mordukowitz is on staff at the Veterans Affairs Medical Center in the Bronx, N.Y.

1. Lytle RA, Reed TE, Pruet RC, Simmons RJ. Hypotony maculopathy following glaucoma filter surgery. American Academy of Ophthalmology meeting paper 1990.
2. Starita RJ, Fellman RL, Spaeth GL, et al. Short and long term effects of postoperative corticosteroids on trabeculectomy. Ophthalmology 1985;92:938-46.
3. Herreras JM, Pastor JC, Calonge M. Ocular surface alteration after long term treatment with an antiglaucomatous drug. Ophthalmology 1992;99:1082-88.
4. Broadway DC, Grierson I, O’Brien C. Adverse effects of topical antiglaucoma medications: The outcome of filtration surgery. Arch Ophthalmol 1994;112:1446-54.
5. Dietze PJ, Feldman RM, Gross RL: Intraoperative application of 5-fluorouracil during trabeculectomy. Ophthal Surg 1992;23:662-65.
6. Kitazawa Y, Kawase K, Matsushita H. Trabeculectomy with mitomycin. A comparative study with fluorouracil. Arch Ophthalmol 1991;109:1693-98.
7. Burney EN, Quigley HA, Robin AL. Hypotony and choroidal detachment as late complications of trabeculectomy. Am J. Ophth 1987;103:685-88.
8. Costa VP, Wilson RP, Moster MR. Hypotony maculopathy following the use of topical mitomycin C in glaucoma filtering surgery. Ophthal Surg 1993;24:389-94.
9. Shields MB, Scroggs MW, Sloop CM. Clinical and histopathologic observations concerning hypotony after trabeculectomy with adjunctive mitomycin C. Am J Ophthalmol 1993;116:673-83.
10. Leen MM, Master MR. Management of over-filtering and leaking blebs with autologous blood injection. Arch Ophthalmol1995;113:1050-55.
11. The Fluorouracil Filtering Surgery Study Group: Three-year follow-up of the Fluorouracil Filtering Surgery Study. Am J Ophthalmol 1993;115:82-92.
12. Speaker MG, Milch FA. Role of external bacterial flora in the pathogenesis of acute postoperative endophthalmitis. Ophth 1991;98:639-49.
13. Orengo-Nania S, El-Harazi SM. Effects of atropine on anterior chamber depth and anterior chamber inflammation after primary trabeculectomy. J Glaucoma 2000;9(4):303-310.
14. Nuyts RM, Greve EL. Treatment of hypotonous maculopathy after trabeculectomy with mitomycin C. Am J Ophthalmol 1994;118:322-31.
15. Zaltas MM, Schuman JF. A serious complication of intrableb injection of autologous blood for the treatment of postfiltration hypotony. Am J. Ophththalmol 1994;118:251-53.
16. Palmberg P, Zacchei AC. Compression sutures: A new treatment for leaking or painful filtering blebs. Invest Ophthalmol Vis Sci 1996;37:S444.
17. Wadhwani RA, Bellows A. Surgical repair of leaking filtering blebs. Ophthalmology 2000;107(9):1681-7.
18. Mietz H, Jacobi P. Postoperative application of mitomycin for trabeculectomies. Arch Ophthalmol 2000;118(10):1341-8.

Antimetabolite Pharmacology
Antimetabolites help reduce postoperative subconjunctival fibrosis and the risk of bleb failure, and increase filtration. Both mitomycin-C (MMC) and 5-fluorouracil (5FU) inhibit fibroblast proliferation and resulting scar tissue formation.

5FU is a pyrimidine analogue that competitively inhibits thymidylate synthase enzyme, interfering with the S-phase of the cell replication cycle. This makes 5FU more toxic to replicating cells than non-replicating cells. Toxicities of 5FU include: corneal and conjunctival epithelial disruption, corneal ulcers, conjunctival wound leaks or subconjunctival hemorrhages.⁵

MMC is an antibiotic isolated from Streptomyces caespitosus that acts independently of the cell cycle to cross link DNA and inhibit cell synthesis. It is 100 times more potent than 5FU and is cytotoxic.^5,6—S.M.

Vol. No: 138:10Issue: 10/15/01