A refined total capsular bag suspension technique for lens subluxation from cystathionine beta-synthase deficiency: A case report and literature review

Abstract

Purpose

To report the application of a refined total capsular bag suspension technique for lens subluxation from Cystathionine beta-synthase (CBS) deficiency.

Observations

A 15-year-old CBS deficiency male patient with a history of intracranial venous thrombosis presented to our clinic due to bilateral vision loss. The patient was treated with lens aspiration, intraocular lens (IOL) implantation, and total capsular bag suspension in both eyes respectively. During the six months postoperative follow-up, the patient exhibited improved visual acuity and minor refractive error.

Conclusions and importance

The refined total capsular bag suspension technique is recommended for CBS deficiency patients with lens subluxation as a safe and effective surgical approach.

Highlights

• •Cystathionine beta-synthase (CBS)deficiency: a rare disorder with ectopia lentis as a common feature.
• •Reports on surgical treatment of ectopia lentis due to CBS deficiency are limited.
• •Our case presents the safety and efficacy of a refined total capsular bag suspension technique for lens subluxation from CBS deficiency.
• •Although no significant complications have been discovered, the long-term efficacy and stability needs to be followed.

1. Introduction

Cystathionine beta-synthase (CBS) deficiency, also known as hyperhomocysteinemia type I or classic homocystinuria (OMIM 236200), is a rare autosomal recessive disorder with a global incidence of approximately 1:1800–1:900,000.¹ Homocysteine (Hcy) is a non-structural amino acid product of the methionine metabolic pathway. CBS deficiency affects the conversion of Hcy to cystathionine, which leads to the accumulation of Hcy. The accumulation of large amounts of Hcy in various tissues throughout the body can cause multisystem complications in the skeletal system, eyes, central nervous system, cardiovascular system, etc. Systemic features of patients include intellectual disability, skeletal deformities (‘marfanoid’ habitus: scoliosis, sternal deformities, arachnodactyly etc.), osteoporosis, and a predisposition to early thromboembolism.¹ Early onset of thromboembolism is the main life-threatening complication of this disease.²

Ectopia lentis is one of the most important clinical features in CBS deficiency.³ Different surgical approaches for ectopia lentis have been reported, such as anterior chamber intraocular lens (IOL) implantation, iris-fixed IOL implantation, sutured or sutureless transscleral-fixated IOL implantation, capsular tension ring fixation with preserved capsular bag, etc., and often combined with vitrectomy when necessary. The conventional scleral-fixated IOL implantation is complicated and time consuming with limited indications. In this case, we report the safety and efficacy of a refined total capsular bag suspension technique for lens subluxation under general anesthesia in a child with a history of intracranial venous thrombosis from CBS deficiency. Furthermore, we summarized previously published reports of patients with ectopia lentis caused by CBS deficiency who underwent ocular surgery.

2. Case report

A 15-year-old male patient presented with bilateral vision loss and was diagnosed with bilateral lens subluxation without any treatment 6 years ago. The patient has a ‘marfanoid’ habitus with arachnodactyly. The patient was diagnosed with CBS deficiency accompanied by intracranial thrombosis in the neurology department one year ago. Afterwards, the thrombosis of the intracranial venous system was cured with conservative treatment by neurologists. The patient's systemic condition was stable when referred to us. The patient has no special past and related family history.

The patient was treated with lens aspiration, IOL implantation, and total capsular bag suspension in the right and left eye respectively (Fig. 1). Table 1 summarizes the results of the ophthalmologic examination before surgery. Oral warfarin was replaced with low molecular heparin 4000u q12h subcutaneously before eye surgery to lower the risk of perioperative bleeding and resumed after surgery if no signs of bleeding were seen.

Fig. 1.

Illustration of the total capsular bag suspension technique, showing how the capsular bag is suspended and fixed in the sclera with the IOL inserted in it.

Table 1.

The results of the ophthalmologic examination before surgery.

	Right eye	Left eye
Optometric examination (six years ago)	20/66 (−6.0/-0.75 × 180°)	20/66 (−4.50/-1.25 × 160°)
Optometric examination (recent visit)	20/133 (−13.50/-2.50 × 45°)	20/100 (−11.00/-2.00 × 155°)
Anterior chamber depth (ZEISS IOLMaster700)	2.60mm	2.60mm
Axial length (ZEISS IOLMaster700)	24.89mm	23.99mm
Corneal curvature (ZEISS IOLMaster700)	K1:41.68D@1 K2: 43.36@91	K1:41.56D@157 K2: 42.73D@67
IOP	13 mmHg	13 mmHg
Slit lamp examination	Pupils were round in both eyes, light reflex was slightly retarded. The lens of both eyes were clear and significantly dislocated inferiorly and nasally. Iridodonesis was seen in both eyes, and slight protrusion of iris in the inferior nasal quadrant. No abnormal findings in the vitreous and retina.

Abbreviations: IOP, intraocular pressure.

The operation was carried out under general anesthesia after complete dilation of the pupil (Fig. 2A). After continuous curvilinear capsulorhexis (Fig. 2B), four iris hooks were placed along the edge of the capsule to pull the anterior capsule opening and stabilize the capsule (Fig. 2C). The lens material was aspirated after hydration and separation (Fig. 2D). A capsular tension ring (13mm) was implanted for additional stabilization and the IOL (ZEISS CT LUCIA 601P/PY, OD+19.50D，OS+22D) was implanted in the capsule bag (Fig. 2E and F). The four iris hooks were then removed. Subsequently, the procedural steps for total capsular bag suspension are carried out (Video 1). Corneal paracentesis was made at 9 o'clock position with a 30G needle. The suspension suture (6-0 polypropylene nonabsorbable suture, Polypropylene, PROLENETM, Ethicon, LLC) was inserted into the anterior chamber through the side port at 9 o'clock position. Then, a 30G needle was inserted 2mm posterior to the limbus at the 2 o'clock position, the end of the suture was docked into the lumen of 30G needle and pulled to the side port at 2 o'clock position 2 mm posterior to the limbus (Fig. 2G). After threading the 6-0 suture, it is continuously guided by the 30G needle and buried in the sclera lamella in a clockwise direction parallel to the limbus for approximately 4mm. (Fig. 2H and I). The other end of the suture was bent and heated at the top of the bend to make it into a narrow U-shape and hooked the edge of capsulorhexis at 1：30 position (Fig. 2J and K). The same method was used to fix the other two hooks at 5:30 and 9:30 positions respectively (Fig. 2L). After checking the centration of the lens and capsular bag, the three ends of sutures were cut at the conjunctival side (Fig. 2M and N).

Fig. 2.

The procedure of the refined total capsular bag suspension technique. (A) Complete dilation of the pupil. (B) Continuous curvilinear capsulorhexis. (C) Placement of iris hooks along the edge of the capsule. (D) Aspiration of the lens material. (E and F) In the bag implantation of capsular tension ring and IOL. (G) The suspension suture at 9 o'clock position. (H and I) The suture was buried in the scleral lamella. (J and K) The other end of the suture was bent and heated at the top of the bend to make it into a narrow U-shape and hooked the edge of capsulorhexis at 1：30 position. (L) The same method was used to fix the other two hooks at 5:30 and 9:30 positions respectively. (M and N) The three ends of sutures were cut at the conjunctival side.

Local antibacterial and anti-inflammatory medications were administrated postoperatively. The patient's visual acuity was 20/33 and the IOLs were well centered in both eyes first day after the surgeries. The intraocular pressure (IOP) of both eyes were normal. The optometric examination after six months was 20/20（-1.25 × 165°) (right eye) and 20/20（+0.25/-1.00 × 160°) (left eye).

The IOLs of both eyes were located within the capsular bag, well centered, no tilt, the three capsular bag hooks were in place in both eyes, with no loosening. No postoperative complications, such as corneal endothelial decompensation, vitreous displacement, and retinal detachment occurred. The general condition was good, and there were no potential risks of general anesthesia such as thrombotic events.

3. Discussion

CBS deficiency is a rare disease that can be treated and prevented. Without timely intervention, 82% of pyridoxine nonresponsive patients will develop ectopia lentis by age 10, 27% will have thromboembolic event by age 15, and 23% will not live beyond age 30.³ Ectopia lentis is the most consistent clinical features in CBS deficiency and many cases have been diagnosed because of this.³ The ocular manifestation, as a hallmark with clear symptoms, relatively early appearance and convenient to be examined, can play a key role in the detection and treatment of this disease, which needs to be understood and paid attention by ophthalmologists. Therefore, when a patient presents with an ectopia lentis that dislocated inferiorly or nasally, iridodonesis, and the ‘marfanoid’ habitus, the diagnosis of CBS deficiency should be considered. The serum homocysteine concentration should then be tested when the traumatic injury is excluded. The family history and genetic evaluation are important and advised.

The ocular managements of this disease can be conservative or surgical. Patients with no significant loss of visual acuity or other pathologic conditions can simply be followed and observed. Hua et al. reported a case of CBS deficiency with secondary glaucoma due to lens dislocation in the anterior chamber, which was successfully treated with IOP-lowering and pupil-dilating medications in order to avoid the risk of thrombosis during general anesthesia.⁴ However, a related study showed that in 37 eyes with anterior chamber dislocation, initial conservative treatment failed and surgery was ultimately required.⁵ Improvements of anesthesia technique have made surgeries for patients with homocystinuria safer.⁶ Several studies have reported that children with this disease can successfully survive the perioperative period under general anesthesia.^7,8

Different surgical approaches for ectopia lentis have been reported.⁹ We summarize and present previously published reports of patients with ectopia lentis caused by CBS deficiency who underwent ocular surgery (Table 2). The major differences between various surgical approaches are whether the capsular bag is preserved, the location of the lens implantation and the methods of IOL fixation. Most of these patients had improved visual acuity after ocular surgery, but some were unable to cooperate with visual acuity examinations because of the intellectual disability, as well as several patients who developed postoperative ocular or even systemic complications.

Table 2.

Literature review of ocular surgical treatment of patients with ectopia lentis caused by CBS deficiency.

Author	Year	Location	Number of subjects	Number of eyes	Associated ocular manifestations	Surgical approach	Surgical complications	BCVA change
Sabrane et al.15	2019	Morocco	1	2		Lensectomy with vitrectomy		Unknown
Gus et al.16	2018	Brazil	1	2	Keratoconus	Lensectomy with vitrectomy		2 improved
Yaqub et al.17	2016	Pakistan	1	2	Iridodonesis	Lensectomy with scleral fixation of IOL		1 improved
Cheng et al.18	2007	Taiwan	1	2	Myopia Glaucoma	Intracapsular lens extraction		Unknown
Smith et al.19	1999	England	1	1	Corneal edema Phacolytic glaucoma Uveitis	Pars plana vitrectomy Lensectomy Trabeculectomy		1 improved
Harrison et al.5	1998	USA	Unknown	65	Optic atrophy Iris atrophy Anterior staphyloma Lens opacity Corneal opacity Retinal detachment Glaucoma	1. Pars plana lensectomy with vitrectomy (20 eyes) 2. Anterior approach lensectomy with vitrectomy (33 eyes) 3. Anterior approach lensectomy without vitrectomy (12 eyes)	change of procedure during the surgery cortical remnants transient right hemiparesis	Unknown
H. Gerding20	1998	Germany	1	2	Cataract Intermittent exotropia Iridodonesis	A new surgical approach （see reference text for details)		2 improved
Bhatti et al.21	1996	India	1	1	Glaucoma	Lensectomy with scleral fixation of IOL	Intraocular hemorrhage Cerebral venous Thrombosis	Unknown
Hayasaka et al.22	1984	Japan	1	2	Glaucoma Iridodonesis	Lens extraction		2 improved
Cross et al.23	1973	USA	Unknown	37	Glaucoma Strabismus Retinal changes Blue sclerae Spherophakia central retinal vein occlusion Microdisk	1.Intracapsular extraction of lens (15 eyes) 2.Discussion and aspiration (6 eyes) 3.No data available (16 eyes)	Vitreous loss Vitreous to the wound Iris prolapse Macular edema Corneal edema Endophthalmitis Retinal detachments	8 improved 7 unchanged 4 worse 5 unknown but fincal acuity 20/30 or better 13 not recorded

The complete surgical removal of the lens often requires combined vitrectomy, which is more traumatic, and has a chance of vitreoretinal complications such as vitreous hemorrhage, retinal detachment etc.^10,11 In this case, the lens capsular bag was preserved, which minimized the interference of vitreous. A capsular tension ring was implanted to provide additional support for the capsular bag. The iris hooks were used to further stabilize the capsular bag, which had made irrigation and aspiration process safer.

Conventional anterior chamber IOL implantation or iris fixation IOL operation have been reported with a number of potential complications, such as corneal endothelial decompensation, peripheral anterior synechiae, iris depigmentation, and secondary glaucoma.¹² Besides, the range of indications for anterior segment IOL implantation is limited and there are a number of ocular conditions that need to be considered, such as the integrity of iris, pupil diameter, anterior chamber depth, corneal endothelial cell density etc.

The posterior chamber IOL implantation conforms to the original anatomy and has good visual effect. Posterior chamber IOL can be placed in the ciliary sulcus when there is peripheral capsular support. In the absence of posterior capsule support, transscleral suture-fixed IOL implantation is preferred, with fixation options including knotted or knotless. Ciliary sulcus IOL implantation or sutureless intrascleral fixated IOL Implantation, can cause long-term chronic inflammation and discomfort.¹³ The standard scleral flap technique typically uses a 10-0 polypropylene suture for two-point fixation of the IOL. This technique requires conjunctival and scleral flaps, carrying the risks of long-term knot erosion and late endophthalmitis. In our case, we only buried the suspension suture in the scleral lamella tunnel for 4 mm and then cut the suture end with slight pressure. This knotless surgical approach is not only firm but also time-saving, which can minimize long-term problems related to knots. A previous article reported the effective use of a similar capsular bag suspension technique in the treatment of lens subluxation caused by pseudoexfoliation, glaucoma and trauma.¹⁴ This implies that the capsular bag suspension technique may be applicable in addressing lens subluxation resulting from various etiologies. Unlike lens subluxation from trauma, the degree of subluxation from CBS deficiency might be further worsened due to progressive pathologic zonular degeneration. The long-term fixation is important. In our case, the three-point total capsular bag suspension technique provides an equilateral triangle with uniform forces in all directions, achieving the most stable structure with the least number of fixation points, although the long-term result needs to be observed. Instead of the 5-0 polypropylene suture commonly used in other capsular bag suspension techniques and the 10-0 polypropylene suture used in the standard scleral flap technique, a 6-0 polypropylene was used in our case. This suture is thinner and less invasive than the 5-0 suture, addressing the biodegradation risk associated with the 10-0 suture and minimizing the cutting force impact on the sclera.

Some limitations still exist regarding this refined surgical technique. Firstly, although we have followed the patient for up to six months without adverse events, there remains a potential risk of suture protrusion or loosening in the longer term. Furthermore, in comparison to the traditional transscleral-fixated IOL technique, the refined bag suspension technique requires the complete preservation of the lens capsule during the aspiration, demanding a higher surgical skill.

4. Conclusions

In conclusion, CBS deficiency is a rare autosomal recessive disorder that can involve multiple system. Ectopia lentis is the most consistent clinical features in CBS deficiency. Total capsular bag suspension can be considered as a safe and effective surgical approach for CBS deficiency patients with lens subluxation. Our refined technique which is easy and less invasive offers sufficient support for both capsule and IOL. Although no significant complications have been discovered, the long-term efficacy and stability needs to be followed.

Patient consent

The patient's legal guardian consented to publication of the case in writing.

Funding

No funding or grant support.

Authorship

All authors attest that they meet the current ICMJE criteria for Authorship.

CRediT authorship contribution statement

Yuezhu Lu: Writing – review & editing, Writing – original draft, Visualization, Validation, Project administration, Methodology, Investigation, Formal analysis, Data curation, Conceptualization. Yang Jiang: Writing – review & editing, Validation, Supervision, Data curation, Conceptualization. Zaowen Wang: Writing – review & editing, Validation, Supervision, Data curation, Conceptualization.

Declaration of competing interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Appendix A. Supplementary data

The following is the supplementary data related to this article: