Diverse presentations of ectopia lentis and lens coloboma in Marfan’s syndrome

Abstract

Marfan’s syndrome (MFS) is an autosomal dominant connective tissue disorder with defect in the fibrillin-1 gene. The most common ocular manifestation is subluxated lens in the superotemporal direction, accounting for 50%–85% of total cases. The association of lens coloboma with MFS has been described in literature, but the coexistence of lens coloboma with ectopia lentis is a rare feature. Here, we describe three cases of MFS including a case of bilateral lens coloboma with ectopia lentis: case 1 – a 39-year-old male with inferotemporal lens subluxation in the right eye and superotemporal lens subluxation in the left eye with open-angle glaucoma and high myopia, case 2 – a 15-year-old child with bilateral superonasal lens subluxation with lens coloboma, and case 3 – a 56-year-old female with bilateral lens coloboma. Case 1 and case 2 had clear lenses with good refractive correction; hence, they were optically rehabilitated with contact lenses, whereas case 3 was advised for cataract surgery. It is important to distinguish the lens coloboma from a more common entity, ectopia lentis as former usually remains stable while the latter might need a surgical intervention.

Introduction

The term ectopia lentis was first given by Karl Stellwag, an ophthalmologist from Austria, in 1856.[1] Marfan’s syndrome (MFS) is the most common hereditary cause of ectopia lentis with fibrillin-1 (FBN-1) gene mutation located on chromosome 15. This leads to deficient zonules, structural alteration in the lens capsule, and systemic abnormalities. A bilateral superotemporal lens subluxation is the most common.[2] The two cardinal features of MFS are aortic root aneurysm/dissection and ectopia lentis which are sufficient to make a diagnosis in the absence of FBN-1 gene mutation. The other systemic manifestations of MFS are tall, thin stature, disproportionate arm and limb ratio, high arched palate, pectus carinatum and hind foot deformity, scoliosis, reduced elbow extension, skin striae, pneumothorax, high myopia and specific facial features. These contribute to a ‘systemic score ≥ 7’ as per Ghent 2 criteria which guide the diagnosis along with aortic disease in the absence of ectopia lentis.[3]

Lens coloboma is a less common finding which usually presents unilaterally and inferonasally. The present study describes three cases of MFS associated with both ectopia lentis and lens coloboma, focusing on points to differentiate the two conditions for proper management.

Case Series

Case 1

A 39-year-old male presented with complaints of diminution of vision for the past 20 days with no history of trauma. He underwent cardiac surgery 5 years back for aortic root dilatation and had a family history of MFS and glaucoma. On ocular examination, his unaided distance visual acuity was counting fingers (CF) at 1 m and 6/24 in the right eye (OD) and left eye (OS), respectively, improving to CF at 1 m with −12.00/−0.05 × 150^• correction in OD and 6/12 with −13.0/−0.25 × 30^• correction in OS. His intraocular pressure (IOP) was 30 mmHg in OD and 28 mmHg in OS. Gonioscopy revealed open angles with no pigment deposition in both eyes (OU). On slit-lamp biomicroscopic examination after dilatation, an inferotemporal subluxation in OD and superotemporal subluxation of lens in the OS was noted with stretched zonules [Figure 1a and b]. The magnified view of the stretched zonules showed the presence of iris pigments [Figure 2a]. Dilated fundus examination with indirect ophthalmoscope revealed advanced glaucomatous disc cupping with cup–disc ratio of 0.9:1 in OD and 0.7:1 in OS. Humphrey’s visual field 10-2 analysis of the OS showed only a central island of vision. The patient was visually rehabilitated with contact lenses and started on antiglaucoma drugs. Over the next 2 weeks, his IOP was well controlled with 11 mmHg in OD and 12 mmHg in OS. Prophylactic peripheral iridotomy was done bilaterally to prevent pupillary block glaucoma. The patient is on a regular follow-up since then.

Figure 1.

Slit-lamp photograph of case 1 showing (a) an inferotemporal lens subluxation in right eye (black arrow) (b) superotemporal subluxation in the OS (black arrow) with stretched and pigmented zonules (red arrow). OD: Right eye, OS: Left eye

Figure 2.

Slit lamp photograph showing (a) ectopia lentis with pigmented zonules and no lens notching (yellow arrow) (b) characteristic flattening with lens notching (red arrow) at lens equator indicating lens coloboma (c) maldeveloped and scanty zonules in the area of lens coloboma (white arrow) and normal zonules in the area of ectopia lentis (black arrow)

Case 2

A 15-year-old boy presented with complaints of diminution of vision OU for the past 15 days. There was no history of ocular trauma or surgery. A family history of similar complaints with tall stature was present in the father, suggestive of MFS. On ocular examination, his unaided distance visual acuity was 6/60 and 5/60 in the OD and OS, respectively, improving to 6/12 with correction of +1.75/−3.00 × 135^• in OD and 6/18 with +0.75/−2.00 × 75^• correction in OS. Slit-lamp examination under mydriasis revealed superonasal lens subluxation OU with lens coloboma extending from 6 to 9 o’clock in OD [Figure 3a] and from 5 to 7 o’clock in the OS [Figure 3b]. The edges of coloboma were notched with maldeveloped zonules along with flattened and concave lens equator bilaterally. A striking difference in zonules was noted, i.e., maldeveloped and scanty in the area of lens coloboma while stretched and normal in the area of ectopia lentis [Figure 2b and 2c]. Fundus in both eyes was normal. The child was given soft toric contact lenses for visual rehabilitation and kept on a regular follow-up.

Figure 3.

Slit-lamp photograph of (a) case 2 showing superonasal subluxation with lens coloboma extending from 6 to 9 o’clock in the OD (red arrow) (b) from 5 to 7 o’clock in the OS (red arrow) (c and d) Case 3 showing lens coloboma with inferiorly flattened lens equator from 4 to 7 o’clock in the OD (blue arrow) and OS with the characteristic notch and stretched zonules (blue arrow). OD: Right eye, OS: Left eye

Case 3

A 54-year-old female presented with complaints of diminution of vision in both eyes for the past 1 year. Family history revealed that her father and an elder brother were of tall stature, indicative of MFS. No history of ocular trauma or surgery was present. On ocular examination, her unaided visual acuity was 6/60 OU improving to 6/12 with −4.0 DS/−2.0 DC × 10° correction in the OD and 6/24 with −6.0 DS/−3.5 Dc × 10° correction in the OS. IOPs were 12 mmHg bilaterally. On slit lamp examination under dilation, a concave and inferiorly flattened lens equator was noted from 4 to 7 o’clock bilaterally with the characteristic notch and stretched zonules, suggestive of bilateral lens coloboma [Figure 3c and d]. Fundus examination with indirect ophthalmoscope was unremarkable. The patient was given refractive correction and advised for cataract surgery in the OS.

All three patients had a positive family history and ectopia lentis with systemic features suggestive of MFS, i.e., tall stature with arm span more than the height, positive wrist and thumb sign, hindfoot and pectus carinatum deformity and high-arched palate with a systemic score of ≥7. The cardiac involvement was present only in case 1. Hence, based on Ghent 2 criteria, a clinical diagnosis of MFS was confirmed in all three cases.

Discussion

Ectopia lentis, the most common feature of MFS, usually remains stable in childhood and progresses in second–third decades, where the risk of pupillary block glaucoma, uveitis, and complete displacement of the lens increases due to zonular laxity. The cause for age related increase in zonular laxity in Marfan’s syndrome remains unknown. However, it has been hypothesized that the product of defective fibrillin-1 gene in Marfan’s syndrome is more prone to degradation by matrix metalloproteinases (MMPs) than normal fibrillin. Hence, due to an imbalance of MMPs and their inhibitors, progressive degradation of lens zonules and subsequent lens subluxation occurs. Further, the peripheral light focusing effect of anterior segment leads to preferential focusing of UV-B light in the inferonasal quadrant of crystalline lens causing weak zonules in that quadrant and hence supero-temporal dislocation.[4] The other ocular manifestations of MFS include retinal detachment, lattice degeneration, strabismus, glaucoma, megalocornea, hypoplastic iris, and ciliary muscle.

Lens coloboma, though a rare feature of MFS, closely resembles ectopia lentis. The lens coloboma occurs secondary to failure of complete closure of the fetal fissure. The zonules in this region are usually absent or maldeveloped either due to the persistence of fibrovascular sheath remnants or optic vesicle’s incomplete closure.[5] A typical coloboma is usually associated with coloboma of the iris, retina, or choroid. But since, etiologically, the lens vesicle is formed independent of fetal fissure closure, lens coloboma is usually an isolated anomaly. The lens is frequently cataractous in coloboma. The cataract is localized to colobomatous area and doesnot involve the foetal or embryonic nucleus.[6] The characteristic feature of lens coloboma is the localized notching with associated flattening and maldeveloped zonules in that area. It is very important to distinguish it from the ectopia lentis, where zonules undergo progressive destruction but are normal in number with no flattening or notching of the lens [Figure 2].

Literature has described the unilateral and bilateral presentation of lens coloboma in MFS, but the bilateral presence of lens coloboma with ectopia lentis is a rare finding.[5,6,7,8,9] Our case series highlight the differentiating points of the two entities, which help in better management of the two conditions. Lens coloboma, usually remains stationary, and if cataract sets in or coloboma involve more than 120°, there is a role of surgical intervention. The phacoaspiration and intra-ocular lens (IOL) with capsular tension ring or Cionni ring implantation in such cases are considered a safe and effective option, as suggested by Gurler et al. in their prospective study.[10]

On the other hand, in ectopia lentis, there occurs progressive destruction of zonules and risk of further complications with increasing age. Hence, peripheral iridotomy is done in earlier stage to prevent pupillary block glaucoma. In case of lens subluxation of more than 50% from pupillary area, pars plana lensectomy with anterior vitrectomy and transscleral fixation of scleral-fixated IOL assisted with fibrin glue has been considered the surgical procedure of choice.[11]

In this case series, case 1 highlights the atypical lens subluxation in the opposite direction in the OD and OS with the need to manage an open-angle glaucoma aggressively in patients with ectopia lentis with frequent follow-ups. Case 2 focuses on the coexistence of coloboma and ectopia lentis and demonstrates that in patients with good refractive correction and clear lens, only a regular follow-up is needed.

Case 3 reiterates the fact that isolated lens coloboma can be a manifestation of MFS and is frequently associated with cataract.

Conclusion

Lens coloboma can be a rare association of MFS with ectopia lentis. Typical notching, concavity of the lens equator, and lack of zonules are diagnostic features of lens coloboma which differentiate it from lens subluxation. An ophthalmologist plays a key role in such patients as timely diagnosis and management can preserve vision and, therefore, enhance the quality of life.

Declaration of Patient Consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient has given his consent for his images and other clinical information to be reported in the journal. The patients understand that his name and initial will not be published and due efforts will be made to conceal his identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

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Conflicts of interest

There are no conflicts of interest.