Case report: Topical pilocarpine ameliorated the accommodation loss and pupillary dilation after micropulse transscleral laser treatment

Abstract

Background

The present study elucidates a common significant postoperative complication of micropulse transscleral laser treatment (mTLT) and explores its potential management strategies for younger patients with good central vision.

Case presentation

Three younger Chinese glaucoma patients with good central vision maintained high intraocular pressures (IOPs) (36, 25, and 30 mmHg) on maximally tolerated topical anti-glaucoma medications. All patients were treated with mTLT because of a higher risk of complications with filtering surgery. After the procedure, their best-corrected visual acuities were not significantly changed, IOPs were significantly decreased, and the number of topical anti-glaucoma medicines was gradually decreased. However, all patients complained about reduced near visual acuity (NVA) for 1–5 months. Slit-lamp examination revealed pupillary dilation, and binocular accommodative function examination indicated accommodation loss. After treatment with 2% topical pilocarpine, all patients reported an improvement in NVA. Among them, we could observe pupillary constriction, recovery of accommodation function, and improved NVA, even discontinuation of pilocarpine in Patient 2.

Conclusion

In younger patients with good central vision, topical pilocarpine might ameliorate accommodation loss and pupillary dilation after mTLT.

Micropulse transscleral laser treatment (mTLT) (IRIDEX Corp., Mountain View, CA) is an alternative approach to glaucoma treatment with laser. Unlike the continuous wave laser used in traditional transscleral cyclophotocoagulation (TSCPC), mTLT employs a noncontinuous delivery mode of an 810 nm diode laser with a duty cycle of 31.3%. The micropulse laser can effectively limit the energy absorption by the ciliary body, minimizing damage and reducing the occurrence of complications. Studies have indicated that mTLT lowers the intraocular pressure (IOP) by reducing aqueous humor production, and increasing aqueous humor outflow through the uveoscleral pathway and the trabecular meshwork pathway [1]. Current reports indicate that, mTLT is effective in lowering IOP in various types of glaucoma with a low incidence of complications. The indications for mTLT are gradually expanding to those with good central vision. The common complications are pupillary dilation [2, 3], cataract progression, and vision loss [4]. However, accommodation loss after mTLT needs detailed exploration. In our report, out of 50 patients who underwent mTLT at Changsha Aier Eye Hospital between September 2022 and August 2023, three patients with pupillary dilation and accommodation loss were identified. This present study reports an mTLT complication accommodation loss and pupil dilatation and its potential effective management.

Case presentation

Patient 1

In November 2022, a 27-year-old Chinese female patient came to the clinic with eye swelling and progressive blurring of vision in her right eye (RE). The IOP (all IOPs were measured using the Goldmann applanation tonometer unless specified) was 36 mmHg RE despite use of three topical anti-glaucoma medications: 0.15% brimonidine tartrate (Alphagan, Allergan Sales LLC, USA) thrice daily, 1% brinzolamide (Azopt, S.A.Alcon-Couvreur N.V, Switzerland) thrice daily, and 2% carteolol hydrochloride (Mikelan, China Otsuka Pharmaceutical Company, Limited, China) twice daily. The IOP in her left eye (LE) was 12 mmHg without medication. Her best-corrected visual acuity (BCVA) was 12/20 RE and 20/20 LE. The near visual acuity (NVA) was J3/30 cm RE and J1/30 cm LE. Slit-lamp examination revealed mild corneal edema, broad peripheral anterior synechiae, and pupil malposition with a diameter of 4.1 mm (all pupil diameters were measured by IOL Master 700, Carl Zeiss Meditec Inc., Germany) in her RE (Fig. 1A). Corneal specular microscopy revealed that the cell density of endothelial cells was significantly decreased to 882 cells/mm² with irregular shape. The left eye was normal. The final diagnosis was iridocorneal endothelial syndrome.

Fig. 1

Slit‑lamp photograph of the right eye in Patient 1 before and after mTLT treatment. (A) showed a pupil deformation in diameter of approximately 4.1 mm before mTLT treatment, and (B) showed the pupil dilated to approximately 4.5 mm after mTLT treatment

Due to the low cell density of the corneal endothelium and the high risk of corneal endothelial decompensation after filtering surgery, we performed mTLT using the Iridex Cyclo G6 Glaucoma system and MicroPulse P3 Probe (IRIDEX Corporation, USA) after obtaining informed consent from the patient (all the mTLT treatment were performed using the same device and the same probe). All procedures were performed in the operating room with retrobulbar/peribulbar block (Lidocaine, Hunan Kelun, China). The probe was held with a firm, steady pressure at 1 mm posterior to the limbus perpendicular over the conjunctival surface with a continuous sweeping motion back and forth for several times (each sweep in one direction was about 15 s) over the superior or inferior hemisphere, avoiding the 3 or 9 o’clock positions.

The parameters used were a wavelength of 810 nm, a treatment duration of 200s, a duty cycle of 31.3%, and a power of 2000 mW, delivering a total of 125.2 J.

On the first day after the procedure, the IOP decreased to 13 mmHg RE without anti-glaucoma medication, and the BCVA recovered to 20/20 RE. However, the patient complained of blurry vision for near with the NVA of J5/30 cm RE. Slit-lamp examination indicated pupillary dilation, with a pupil diameter of approximately 4.5 mm (Fig. 1B). Binocular accommodative function examination revealed accommodation loss in the RE, with an amplitude of accommodation (AMP) of 4 diopter (D) (measured using the subjective push-up method by Phoroptor, Topcon, Japan), a monocular accommodative facility (MAF) of 0 cpm (measured using a flipper and 20/30 Rock Card at 40 cm in front of the eyes), a negative relative accommodation (NRA) of + 2.50D (plus lenses were gradually added to both eyes as 0.25 D steps until first slight sustained blur), positive relative accommodation (PRA) of -2.00D (minus lenses were gradually added to both eyes as 0.25 D steps until first slight sustained blur) and a binocular crossed cylinder test (BCC) of 0D (measured by the crossed-cylinder lens). All binocular accommodative function examinations were performed by the same optometrist with the same method unless otherwise specified. As the BCVA was 20/20, we considered blurry vision to be a transient loss of near vision caused by postoperative inflammation. The patient was prescribed 1% prednisolone acetate (Pred Forte, Allergan Pharmaceuticals, Ireland) every 2 h in the RE, with gradual reduction over three weeks until discontinuation.

About one month after the operation, the patient experienced increased IOP (28 mmHg) in the RE following trauma. We prescribed 1% brinzolamide and 0.5% timolol (Azarga, Alcon-Laboratories, UK) twice daily and 0.15% brimonidine tartrate (Alphagan, Allergan Sales LLC, USA) three times daily. Within five months, the IOP in her RE fluctuated between 12 and 20 mmHg. However, the decreased NVA persisted, and the pupil remained dilated for the entire period. We suggested treating her RE with 2% topical pilocarpine (Zhenrui, Shandong Bausch Lomb, China) once daily RE. She reported significant improvement in near vision after using pilocarpine, but the side effects, including the eye pain and headache, forced her to stop using it.

Patient 2

In November 2022, a 34-year-old Chinese female patient manifested with visual field loss in her RE. She had previously undergone bilateral peripheral laser iridotomy for chronic primary angle closure. At presentation, both eyes demonstrated BCVA of 20/20, NVA of J1 at 40 cm in front of the eyes, and an IOP of 25 mmHg. She was intolerant to all topical anti-glaucomatous medication, including 1% brinzolamide and 0. 5% timolol (Azarga, Alcon-Laboratories, UK) twice daily, 0.15% brimonidine tartrate (Alphagan, Allergan Sales LLC, USA) three times daily, and 0.03% bimatoprost (Lumigan, Allergan Sales LLC, USA) once per night. Slit-lamp examination revealed a shallow anterior chamber, transparent lens, and normal size (3.5 mm in diameter) pupil sensitive to light and accommodation in both eyes (Fig. 2A). Binocular accommodative function tests indicated that the patient’s accommodation function was slightly impaired (AMP of 4.75 D, MAF of 13 cpm in the RE, and AMP of 3.75 D, MAF of 13 cpm in the LE), probably caused by high IOP.

Because of the high risk of malignant glaucoma and the potential need for transparent lens extraction following filtering surgery, we performed mTLT. After obtaining informed consent from the patient, the procedure was performed in the RE with the same parameters as Patient 1.

One day after mTLT, her pupil was dilated to 5.3 mm in diameter with no response to light or accommodation (Fig. 2B). Her BCVA was maintained at 20/20, and the IOP decreased to 10 mmHg without medication. Similar to Patient 1, she complained of difficulty with near vision with NVA of J5/40 cm RE. To alleviate the inflammation, we administered Patient 2 the same dosage of 1% topical prednisolone acetate (Pred Forte, Allergan Pharmaceuticals, Ireland) as given to Patient 1. The use of anti-glaucomatous medication was gradually discontinued.

Fig. 2

The following-up of the right eye in Patient 2. Slit‑lamp photograph (A) showed the conjunctival congestion, and normal-size pupil in diameter of 3.5 mm (measured using IOL Master 700, Carl Zeiss Meditec Inc., Germany) with sensitive response to light and accommodation pre-treatment. One day after the mTLT procedure, pupillary dilation to 5.3 mm with no response to light or accommodation was observed (B). After the 2% topical pilocarpine treatment, the pupillary constriction could be observed. Discontinuation of pilocarpine (7 months after mTLT procedure), the pupil remained narrow (2.8 mm in diameter) but still with no response to light or accommodation (C)

One week after the operation, the accommodation function in her RE decreased significantly, with an AMP of 2.50 D and a MAF of 2 cpm. The pupil continued to dilate (5.80 mm in diameter in the RE) with an IOP of 11 mmHg RE without medication. One month after mTLT, the accommodation loss in the RE (AMP was 3.00 D, and MAF was 4 cpm) and pupillary dilation (5.70 mm in diameter) without response to light or accommodation did not ameliorate spontaneously, and the IOP gradually increased to 21 mmHg without any anti-glaucoma medication. Moreover, she could not tolerate the blurry near vision with NVA of J5/40 cm. After discussion, we prescribed 2% pilocarpine (Zhenrui, Shandong Bausch Lomb, China) once daily, hoping to narrow the pupil and reduce the IOP.

One week after using pilocarpine, her NVA recovered to J1 at 40 cm, the same as pre-intervention. The pupil’s diameter narrowed to 2.6 mm, and the IOP reduced to 14 mmHg. As the pilocarpine may affect the accommodative function examination, we performed the accommodative function examination on a drug-free day. Thus, we changed the dosage of pilocarpine to once every two days. Two weeks after the pilocarpine treatment, the accommodative function in her RE recovered to almost normal levels, with an AMP of 5.50 D and an MAF of 10 cpm. Subsequently, the dosage of pilocarpine was changed to once every three days. Three months after mTLT, the IOP in her RE was 15 mmHg, and the accommodation function had recovered to normal levels, with an AMP of 6.00 D and a MAF of 20 cpm. The same pilocarpine dosage was continued until six months after mTLT. As the pupil’s diameter was 3.00 mm, we attempted to discontinue pilocarpine and replace it with 1% brinzolamide and 0.5% timolol (Azarga, Alcon-Laboratories, UK) once daily. However, one month after this change, the pupil diameter in the RE did not become larger (2.80 mm), with no response to light or accommodation (Fig. 2C). Despite this, the IOP was controlled at 13 mmHg and the accommodation function remained stable, with an AMP of 6.00 D, and a MAF of 20 cpm (Table 1; Fig. 3).

Table 1 The parameter of right eye in patient 2 at 7-month follow-up

Fig. 3

The quantitative changes of the right eye in Patient 2 during the following-up. (A) showed the decreased intraocular pressure after mTLT treatment gradually increased again at month 1, and topical pilocarpine treatment could effectively lower the intraocular pressure. (B) showed topical pilocarpine treatment at week 5 could ameliorate the pupillary dilation after mTLT treatment. (C) showed topical pilocarpine treatment at week 5 could improve the amplitude of accommodation to the normal level after mTLT procedure. (D) showed the impaired monocular accommodative facility after mTLT treatment was improved by topical pilocarpine eye drops

Patient 3

In June 2023, a 44-year-old male patient presented with visual field loss in the RE. His BCVA was 20/20 RE and no light perception LE, with an NVA of J4 at 40 cm in the RE. The IOP was 30 mmHg RE and 50 mmHg LE intolerant to all topical anti-glaucomatous medication, including 0.004% travoprost (Travatan, Alcon Cusi S.A., Spain) once per night, 0.2% brimonidine tartrate and 0.5% timolol (Combigan, Allergan Pharmaceuticals, Ireland) twice daily, and 1% brinzolamide (Azopt, S.A.Alcon-Couvreur N.V, Switzerland) thrice daily. Slit-lamp examination revealed a transparent cornea, shallow anterior chamber, transparent lens, and normal size of the pupil (2 mm in diameter) sensitive to light and accommodation in the RE, and mild corneal edema, and anterior chamber disappeared in the LE. The RE exhibited total glaucomatous cupping, and the fundus of the LE was invisible. Finally, the diagnosis was chronic angle-closure glaucoma in the RE and malignant glaucoma in the LE.

Our previous experience with mTLT in patients with good vision demonstrated good safety and efficacy, and we performed the mTLT on both eyes after obtaining informed consent. The procedure was performed in both eyes, with a wavelength of 810 nm, a treatment time of 240 s, a duty cycle of 31.3%, and a power of 2000 mW, delivering a total of 150.24 J.

The IOP measurements were as follows: on day one, 21 mmHg RE and 40 mmHg LE without medication; after one week, 13 mmHg RE and 18 mmHg LE with the same medication as pretreatment; after one month, 11 mmHg RE with 2% carteolol hydrochloride (Mikelan, China Otsuka Pharmaceutical Company, Limited, China) twice daily and 18 mmHg LE with 1% brinzolamide and 0.5% timolol (Azarga, Alcon-Laboratories, UK) twice daily, and 0.15% brimonidine three times daily. However, one month after mTLT, his VA worsened to 10/20 RE, the BCVA slightly worsened to 18/20 RE, and the RE pupil dilated to 4 mm in diameter with no response to light or accommodation. He complained of near vision problem, with NVA of J6 at 40 cm. We prescribed 2% topical pilocarpine (Zhenrui, Shandong Bausch Lomb, China) once daily for RE. One month later, his VA recovered to 18/20, NVA was J4 at 40 cm and the pupil narrowed to 1.8 mm in diameter with no response to light or accommodation.

Discussion

As a new and alternative modality of laser therapy, mTLT has demonstrated significant advantages, especially for patients at high risk for filtering surgery. Due to the expanded indications of mTLT, more unreported complications can be observed. To our knowledge, our study is the first to describe accommodation loss after mTLT.

Unlike TSCPC, where the laser acts on the pars plicata of the ciliary body, mTLT targets the pars plana [5]. TSCPC is generally only applied to patients with refractory advanced glaucoma. However, mTLT has been gradually applied to those with good vision in the early and middle stages [4]. We prospectively demonstrated detailed information on three young patients suffering from significant difficulty with near vision, accommodation loss, and pupillary dilation after mTLT, but their BCVA was non-significantly changed. Edema and thickening of the ciliary body were observed in the early postoperative ultrasound biomicroscopy of Patient 2, leading us to initially speculate that the accommodation loss was caused by laser-induced tissue edema, resulting in transient dysfunction. However, no significant changes in the ciliary body were observed in Patient 1. Furthermore, in Patient 1, dilated pupil and decreased NVA persisted for five months. Therefore, we believed that drug intervention was needed to improve the NVA in young patients. In Patients 2 and 3, we observed that 2% topical pilocarpine could ameliorate pupillary dilation and accommodation loss. Moreover, the maintenance of accommodation function was still observed after topical pilocarpine was discontinued in Patient 2.

Accommodation refers to the eye’s ability to change its focal point from distant objects to near objects. Additionally, it is mediated by the contraction of the ciliary muscle, which is innervated by the parasympathetic nervous system. When the ciliary muscle contracts, the zonular fibers at the equator of the lens relax, causing the lens to become thicker and increasing its refractive power. Generally, dysfunction in the contraction power of the ciliary muscle contraction or decreased viscoelasticity of the lens are the main causes of accommodation loss [6]. Polizzi et al. [7] reported a case of accommodation loss after retinal photocoagulation. They considered that the thermal injury from the laser caused damage to the short ciliary nerve, which innervates both the ciliary body and the pupillary sphincter. This resulted in an asymmetric contraction of the ciliary muscle and led to a loss of accommodation. When mTLT is performed, the probe needs to slide in an arc along the limbus (in a painting manner) [5]. The ciliary pigment epithelium absorbs the laser energy, causing heat accumulation. Mechanical and thermal injury to the short ciliary nerve may lead to asymmetric contraction of the ciliary muscle and contraction disorder of the pupillary sphincter, resulting in accommodation loss and pupillary dilation.

Pilocarpine, a cholinergic muscarinic receptor agonist, has been gradually used in the treatment of presbyopia [8]. It directly stimulates the muscarinic receptors on the pupillary sphincter and ciliary body, causing the pupillary sphincter to contract and enhancing the depth of focus while also improving accommodation function in ciliary muscle. Price et al. [6] reported in their two randomized phase 2 studies that pilocarpine, at optimal concentrations ranging between 1.16% and 1.32% once daily, significantly increased the NVA. Therefore, pilocarpine holds the potential for treating accommodation loss and pupillary dilation after mTLT. Conversely, Erickson-Lamy et al. [9] tried to remove the ciliary ganglion or postganglionic ciliary nerve in the cynomolgus monkey and observed that the responsiveness to pilocarpine maintained supersensitive for about six months before gradually returning to normal levels. They believed that the ciliary muscles could reinnervate through the regeneration of the parasympathetic pathway. Similarly, Kaufman et al. [10] reported that the accommodative apparatus became supersensitive to pilocarpine following the surgical removal of the posterior ciliary nerves in cynomolgus monkey. Moreover, several weeks after the pan-retinal photocoagulation, regeneration of short ciliary nerves, restoration of nerve terminals, and reorganization of myelinated sheaths could be noted. Thus, we speculate that mTLT treatment could damage the short ciliary nerve, resulting in accommodation loss and pupillary dilation. Pilocarpine could then directly bind to and activate muscarinic M3 receptors to contract iris sphincter muscles and ciliary muscles, thereby improving near vision. After several months, accommodation function could be maintained even after discontinuing topical pilocarpine, due to the regeneration of the parasympathetic pathway. However, further clinical experience and fundamental experiments are required to substantiate the specific mechanism, which remains unknown.

Conclusion

The surgical treatment of younger glaucoma patients with transparent lenses and shallow anterior chambers presents certain challenges. Our case studies have demonstrated that mTLT has a good efficacy in reducing IOP with minimal invasion. However, it is crucial to be cautious and mindful of the potential effect on accommodation function and pupillary dilation in younger patients with good central vision. Topical pilocarpine may assist in the recovery of accommodation function and pupillary dilation.