Corneal Endothelial cell changes after sub scleral Trabeculectomy in glaucoma patients

doi:10.21203/rs.3.rs-2476259/v1

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Corneal Endothelial cell changes after sub scleral Trabeculectomy in glaucoma patients

https://doi.org/10.21203/rs.3.rs-2476259/v1

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Background: About 1% of the population over the age of 40 develops glaucoma, making it the most common cause of irreversible blindness. Seventy-four per cent of all glaucoma cases are primary open-angle glaucoma. Trabeculectomy is a form of modern filtration surgery used to lower intraocular pressure in a glaucoma patient.

Aim of the Work: evaluation of corneal endothelial cells changes before and after sub scleral trabeculectomy using specular microscopy.

Patients and Methods: Our study was a prospective non-randomized study of 20 glaucomatous patients managed by trabeculectomy with Mitomycin C, the study included patients above the age of 40 years with open angle glaucoma that failed to be controlled by medical treatment. We compared the preoperative and postoperative central corneal endothelial cell density (ECD), endothelial cell coefficient of variation (CV), Hexagonal cell percentage, corneal thickness, best-corrected visual acuity, and intraocular pressure (IOP).

Results: our study revealed a highly significant decrease in central corneal endothelial cell count following trabeculectomy, the suggested mechanisms may be the toxic effect of MMC, increased manipulation in the anterior chamber during surgery and fluctuation of IOP following surgery

Conclusion: According to our findings, the central corneal thickness hardly budges after trabeculectomy, and the fraction of hexagonal cells decreases.

Corneal Endothelial Cell Count

Trabeculectomy

About 1% of the population over the age of 40 develops glaucoma, making it the most common cause of irreversible blindness. Seventy-four per cent of all glaucoma cases are primary open-angle glaucoma. Trabeculectomy is a filtration surgery used to lower intraocular pressure and is the main surgical treatment in a glaucoma patient.¹ although it is a safe procedure but many complications can occur such as hypotony, choroidal detachment, and anterior chamber collapse which can affect the corneal endothelium, Corneal decompensation was reported as a late postoperative complication after trabeculectomy. ²

In healthy corneas, the endothelium forms a monolayer of polygonal cells (mostly hexagons) of consistent size and shape. Its principal role is to control corneal water content via active ion transport.³ Corneal oedema and diminished visual acuity are risk factors for changes in this hydration. Safeguarding these cells is crucial due to their essential function in vision and extremely limited regeneration capacity. Endothelial cell density (ECD) in humans is 5000–6000 cells/mm2 at birth and declines to 2500–3000 cells/mm2 in adulthood .⁴

Specular microscopy is a noninvasive photographic technique that visualizes and analyzes the corneal endothelium. Using computer-assisted morphometry, it can analyze the size, shape and population of the endothelial cells. It is valuable as a marker for endothelial function, even though ECD is an indirect marker and not a perfect reflection of physiological function, it is possible that once ECD falls below a critical level and/or under conditions of physiologic stress, the underlying functional reserve will be insufficient to maintain the proper corneal hydration status and corneal clarity.⁵

When the number of endothelial cells decreases, the surviving cells grow to fill the voids left by the dead ones; this causes a shift in the size (polimegatism) and shape (pleomorphism) of the remaining cells.⁶ Vision impairment and corneal oedema occur when the cell density of the cornea drops below 400 to 700 cells/mm².⁷

Increased intraocular pressure (IOP) is a common finding of glaucoma, and this increase has been linked to both the health of the corneal endothelium and the accelerated death of corneal endothelial cells in glaucoma so the endothelium lining the cornea is vulnerable to damage by the glaucoma disease process or by the treatment as well.⁸

The aim of the present study was to evaluation of corneal endothelial cell changes before and after sub-scleral trabeculectomy using specular microscopy.

Inclusion criteria: Any patient with chronic open-angle glaucoma that failed to be controlled by medical treatment and planned for sub-scleral trabeculectomy.

Exclusion criteria: Neo-vascular Glaucoma patients, any other ocular diseases besides glaucoma, corneal opacities, degeneration or dystrophies (endothelial cell dystrophies such as corneal guttata, pseudo ex foliating glaucoma, and pigment dispersion syndrome.

Methods:

It is a Prospective non -randomized study on 20 glaucomatous patients planned to undergo sub-scleral trabeculectomy. All cases were examined in Al Zahraa university hospital Cairo, Egypt except the corneal examination was evaluated by specular microscopy at Bab Al Shaareya Hospital Al-Azhar University. All study participants gave written informed consent before enrolment, in addition to the usual surgical consent. The study was approved by the Ethics Committee of Al-Azhar university.

Preoperative evaluation:

A detailed eye examination is done on every patient including the following:

A-Taking Full history: name, age, sex, types and the number of glaucoma medications and history of intraocular or extraocular surgery that involved the conjunctiva was recorded.

B-Complete ophthalmological examination including:

Best corrected visual acuity (BCVA) measured using a Landolt’s C chart and expressed in Log Mar scoring, slit-lamp examination, fundus examination with optic disc evaluation by Volk 90 Diopter lens, intraocular pressure recording (using the Goldmann’s applanation tonometry), gonioscopy: using the Goldmann 3-mirrors contact goniolens,

non-contact specular microscope for evaluating the corneal endothelium by Topcon sp-1p, (Topcon Medical Inc., Japan). Images were examined by in-built software that measured corneal metrics: central endothelial cell density ECD (cells/mm²) The rate of polymegethism is represented by the coefficient of variation (CV), percentage of hexagonal cells HEX, (If a patient’s corneal endothelium demonstrates less than 50% hexagonally-shaped cells, this is considered clinically significant pleomorphism) and central corneal thickness CCT.

Trabeculectomy: All the cases were done by the same surgeon using the same instrument, retro bulbar anaesthesia with lidocaine 2% then fornix-based conjunctival flap was created, a 0.2 mg/mL solution of mitomycin C (MMC) was applied for 3 min, followed by irrigation with a balanced salt solution then rectangular flap was created.

Postoperative follow-up: The first day after surgery then after one week and after one-month evaluation by slit lamp to detect any complication and assessment of the IOP together with specular microscopy to detect corneal endothelial cell count, density ECD, the coefficient of variation (CV), Hexagonal cell percentage and corneal thickness. There were 3 postoperative follow-up visits within one month of surgery: 1 day, 1 week and 1 month postoperatively.

Statistical methods:

SPSS, a statistical program for the social sciences, version 28, was used for data entry and coding (IBM Corp., Armonk, NY, USA). Averages and standard deviations were calculated for numerical variables, whereas counts and percentages were used to summarize categorical data. The significance level was set at a p-value of less than 0. 05.

The study included 20 patients with chronic open-angle glaucoma candidate for sub scleral 11 males and 9 females, 5 of them revealed positive family history. the mean age of the study group is 50.85(range 40–62).

Clinical evaluation:

The mean IOP in the study group was 28.4 mmHg preoperative and become16.mmHg. By comparing the preoperative and postoperative data, it revealed a highly significant lowering in IOP,

the VA is slightly improved after surgery but the change in visual acuity was not statistically significant (p-value = 0.037).

The CCT slightly increased after surgery but the change was statistically non –significant,

As regard, corneal endothelium:

the central corneal Cell density and HEX% is decreased significantly after surgery, and. While significant increase in coefficient of variation CV as shown in table (1).

Table 1

Comparison between preoperative and postoperative data
	Preoperative		Postoperative		P value	Sig.
	Mean	SD	Mean	SD	P value	Sig.
IOP	28.45	6.75	16.05	4.56	< 0.001	HS
VA	0.34	0.22	0.38	0.23	0.037	S
CCT	515.30	30.85	519.70	29.68	0.109	NS
Cell density	2775.95	428.85	2497.65	466.80	< 0.001	HS
HEX (%)	39.45%	6.03	34.70%	5.73	< 0.001	HS
CV	30.95	3.61	38.95	7.77	< 0.001	HS

Our study was a prospective non-randomized study on 20 glaucomatous patients managed by trabeculectomy with Mitomycin C to evaluate the effect of surgery on the corneal endothelium. we used a non-contact specular microscope (Topcon sp-1p, Topcon Medical Inc., Japan) to measure ECD (cells/mm2), CV in cell size, HEX%, and CCT.

By comparing the preoperative and postoperative data, it revealed a very significant decrease in IOP, Cell density, and HEX % with an increase in CV, while there is a non-significant change in corneal thickness following trabeculectomy, Pillunat et al.¹⁰ reported in his study Trabeculectomy can significantly lower intraocular pressure (IOP), although it does not affect the structural tissue qualities of the cornea.

Omatsu et al. ¹¹ support us as post-operatively, the IOP dropped dramatically. The average intraocular pressure (IOP) in the trabeculectomy group decreased from 18.3 ± 8.7 mmHg at baseline to 9.8 ± 3.6 mmHg at 6 months, 10.9 ± 4.3 mmHg at 12 months, 10.9 ± 4.3 mmHg at 18 months, and 11.2 ± 4.8 mmHg at 24 months. At baseline, the mean CECD in the trabeculectomy group was 2505 ± 280 cells/mm2, but by months 6, 12, 18, and 24, this number had dropped to 2398 ± 274 cells/mm2 (P < 0.001), 2349 ± 323 cells/mm2 (P 0.001), 2293 ± 325 cells/mm2 (P < 0.001), and 2277 385 cells/mm2 (P = 0.003).

The specific mechanism responsible for the endothelial cell loss following trabeculectomy has yet to be fully clarified and is likely multifactorial. Several potential reasons have been hypothesized for the reductions in CECD after trabeculectomy. Despite evidence that MMC is harmful to the corneal endothelium, postoperative complications like poor IOP regulation and greater anterior chamber manipulation persist. A decrease in CECD was seen in several trabeculectomy studies without the use of MMC. Inferring then that other factors may be involved in the endothelium damage that has been seen.¹²

Dios et al. ¹³ reported in his study that Statistically significant (p < 0.001) reductions in mean endothelial cell density (ECD) of 464 cells/mm2 (17.86%) at 30 days post-surgery and 563 cells/mm2 (21.67%) after 120 days were observed. No significant reduction in ECD was seen between patients who had whole success (IOP 18 mm Hg postoperatively) and those who had partial success or failure (26.08 percent and 29.4 per cent, respectively; p < 0.001). Complications after surgery, such as hyphema or a flat anterior chamber, were associated with a greater decrease in ECD than were complications-free individuals (-1059 vs -456 cells/mm2; p 0.001). Pseudophakic individuals also had a lower ECD than those who had never had cataract surgery (-571 vs. -405 cells/mm2; p < 0.001). In agreement with our findings, the CV was found to be significantly higher in nearly all patients, despite differences in IOP value, complications, and lens status.

He concluded finally that Postoperative time, inadequate intraocular pressure control following trabeculectomy, postoperative problems (such as a flat anterior chamber), and a history of cataract surgery were all linked to a more severe loss. Almost all patients had an elevated CoV count, and there was no clear risk factor increase. Our findings lend credence to the idea that risk factors for corneal injury ought to be taken into account when determining surgical care for glaucoma, with the aim of preventing surgical complications.¹³

Also in Hirooka et al.¹⁴ study, the average CECD was 2420357 cells/mm2 before surgery, and it dropped significantly to 2276400 cells/mm2 at 6 months, 2290 ± 398 cells/mm2 at 18 months, and 2267 ± 446 cells/mm2 at 24 months (p0.001). After observing a 10% drop in CECD at 6, 12, 18, and 24 months post-op, he concluded that CECD dramatically and persistently decreased after trabeculectomy.

Okumura et al. ¹⁵ study trabeculectomy, which was performed on 51 eyes belonging to 37 glaucoma patients. Through the use of contact specular microscopy, the CEC density was calculated. Slit-scanning wide-field contact specular microscopy showed that the average CEC densities of all eyes on the side of the bleb opposite the bleb, in the centre of the cornea, and near the bleb were 2210, 1930, and 1519 cells/mm2, respectively, indicating a significantly lower CEC density near the bleb than at the other two sites. The coefficient of variation (a clinical indicator of polymegathism) was consistently 0.38 in the region surrounding the bleb, which was much higher than the bleb's core and the bleb's opposite side (0.32 and 0.33, respectively). Near the bleb, there was a markedly smaller percentage of hexagonal cells (a clinical signal of polymorphism) than in the middle (54.9 and 60.4 percent, respectively).

Our results revealed decreased central corneal cell density and percentage of hexagonal cells following trabeculectomy and increased coefficient of variation while the central corneal thickness shows insignificant changes.

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No competing interests reported.

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Corneal Endothelial cell changes after sub scleral Trabeculectomy in glaucoma patients

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Patients And Methods

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Clinical evaluation:

Discussion

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