Retinal detachments associated with choroidal colobomas

Abstract

To summarize the characteristics of the retinal detachments (RDs) that are associated with choroidal colobomas that occur in pediatric and adult patients. A choroidal coloboma is a rare disorder that results from an incomplete closure of the embryonic optic fissure, and their size can range from small colobomas with isolated chorioretinal involvement to large colobomas affecting the iris, choroid, retina, and optic nerve. A RD is occasionally associated with choroidal colobomas, and histological studies of the area of the choroidal coloboma show an absence of normal choroidal tissue, retinal pigment epithelium (RPE), and retina. Near the margin of the coloboma, the inner retinal layer has a central continuation of the marginal intercalary membrane (ICM) within the coloboma. The outer layer folds back, becomes disorganized, and fuses with the RPE. The inner retina gradually thins and merges with the marginal ICM with a high incidence of tears of the ICM developing along the edge of the coloboma or toward the center. Because of the high association of the causative retinal breaks being located within the colobomatous area, vitrectomy, endolaser photocoagulation around the margin of coloboma, and long-term tamponade with silicone oil or gas are recommended treatments. In addition, the presence of the macula within the area of the laser photocoagulation should be considered. However, the recurrence rate is high and multiple surgeries are required to reattach the detached retina.

Introduction

A choroidal coloboma is a rare ocular disorder that results from an incomplete closure of the embryonic fissure during the 6^th to 7^th week of gestation. It occurs in only 0.14% of the general population.[1,2,3,4,5] The closure of the embryonic fissure begins in the inferior equatorial region and progresses to the periphery and the posterior pole of the eye. When an incomplete closure of the embryonic fissure occurs, the choroid and retinal pigment epithelium (RPE) in the colobomatous area is defective. Sixty percentage of colobomas are reported to be bilateral.[5,6] The retina becomes thin and hypoplastic in the coloboma lesion, and the sclera is often also thin. Choroidal colobomas may also be associated with colobomas of the eyelid and iris.[5,6]

The clinical findings of choroidal colobomas are varied. The coloboma lesions range from small, longitudinally oval defects that are present just below the optic disc to defects extending from the optic disc to the lower irido-pupillary region.[3,5] The defect is longitudinally oval and white due to the lack of pigmented tissue. The choroid and sclera can be displaced inferiorly due to the thinning, and small anomalous retinal vessels may be seen within the depression. The coloboma lesion can also include the optic disc. A choroidal coloboma can be associated with other ocular abnormalities such as microphthalmia, cataracts, and myopia[3,4,5,6,7,8] and genetic disorders such as the CHARGE syndrome (coloboma, heart abnormalities, anal atresia, renal abnormalities, genitourinary abnormalities, eye abnormalities),[9,10,11,12,13] the Goldenhar syndrome,[14,15,16] the Rubinstein-Taybi syndrome,[17] the Edwards’ syndrome (trisomy 18),[18,19] the Wolf Hirschhorn syndrome,[20] the basal cell nevus syndrome,[21] the Aicardi syndrome,[22,23] congenital rubella,[24] and the Joubert syndrome.[25,26,27]

Gopal et al.[2] evaluated 67 eyes of 40 patients with fundus coloboma and identified six types of colobomas with disc involvements: (I) normal disc outside the fundus coloboma (27.8%); (II) abnormal disc outside the fundus coloboma (10.4%); (III) colobomatous disc outside the fundus coloboma (8.9%); (IV) normal disc within the fundus coloboma (5.0%); (V) colobomatous disc within the fundus coloboma (44.3%); and (VI) disc shape not identified but blood vessels seen emanating from the superior border of the large fundus coloboma (2.9%). The visual acuity was better in types I, II, and III than in the IV, V, and VI colobomas. Microphthalmos was more common in the more severe colobomas. High myopia was more common in the less severe colobomatous anomalies.

Clinical Presentations

The prevalence of retinal detachment (RD) associated with choroidal coloboma ranges from 17.6% to 43%.[4,28,29] Daufenbach et al.[4] evaluated 86 eyes of 48 patients with a choroidal coloboma, and they reported that the ocular involvement varied from small colobomas with isolated chorioretinal anomalies to large colobomas affecting the iris, choroid, retina, and optic nerve. The mean age at the initial and the most recent examinations was 27 months and 100 months, respectively. The average follow-up duration was 6.1 years. Six RDs (8.1%) were found in four patients.[4] The age of the patients when the RD was detected was 5 months, 29 months, 10 years, and 15 years. A choroidal detachment was found in a child at age 9 years of age. The incidence of a combined retinal or choroidal detachment was 10.4% of patients and 8.1% of affected eyes. Thirteen eyes were microphthalmic and six had a microcornea. Eighteen patients (38%) had other systemic abnormalities. Uhumwangho and Jalali[29] reported that 87.2% of eyes with choroidal coloboma had other ocular abnormalities including an iris coloboma (71%), microcornea (45.1%), nystagmus (41.5%), strabismus (21.2%), and microphthalmos (19.1%).

Gopal et al.[30] evaluated 36 eyes of 36 patients with RDs that extended into the choroidal coloboma. They found that the RDs that extended into the colobomatous area were always associated with tears in the fragile appearing tissue within the coloboma. Based on the identifiable breaks within the coloboma and the extent of the RD, three distinct types of breaks were identified within the coloboma: (1) breaks at the edge of the detachment within the coloboma, (2) oval atrophic breaks, and (3) breaks in the anatomic macula that was involved in the coloboma. Commonly, the breaks are seen at the edge of the RD within the coloboma or as oval breaks within the detached fragile appearing tissues. Multiple breaks were common.

Hussain et al.[31] evaluated 15 eyes with a RD associated with a choroidal coloboma. Four (27%) of these 15 eyes had retinal breaks within the coloboma, 5 eyes (33%) had retinal breaks outside the coloboma, 2 eyes (13%) had retinal breaks both within and outside the coloboma, and the retinal breaks could not be localized in 4 eyes (27%). Abouammoh et al.[32] reported that the primary retinal breaks were located within the coloboma in 58.5% of 119 eyes that underwent vitrectomy for a RD associated with the choroidal coloboma. Kannan et al.[33] reported that breaks in the colobomatous region were detected in 16.1%, peripheral breaks in 38.7%, and both types in 9.7%. Hocaoglu et al.[34] reported that the retinal breaks were located within the coloboma in 40% and both within and outside the coloboma in 10% of the 10 eyes.

An association has also been found between chorioretinal colobomas and choroidal neovascularization (CNV) that occur at the temporal margin of the coloboma through defects in Bruch’s membrane.[3,4,35] Grewal et al.[35] examined 8 eyes of eight patients with a mean age of 4.1 ± 3.9 years (range 6 months to 10 years) from a study of children < 16 years of age. All had undergone optical coherence tomography (OCT) imaging for CNV and chorioretinal and optic nerve coloboma. An optic nerve coloboma was present in two eyes and combined optic nerve and chorioretinal coloboma in six eyes. In all eyes, the CNVs were located at the temporal edge of the coloboma closer to the macula. The OCT images showed subretinal fluid in 5 eyes, intraretinal fluid and cysts in 1 eye, and subretinal hyperreflective material in 7 eyes. Genetic or systemic abnormalities were detected in 6 patients.

Pathology

Histologically, the region of the choroidal coloboma lacked the normal choroid, retinal RPE, and retina.[36,37,38,39] In the developing retina of coloboma patients, the inner retinal layer has a central continuation of an intercalary membrane (ICM) to the coloboma, and an outer retinal layer that folds back, becomes disorganized, and fuses with the RPE near the edge of the coloboma. The inner retina gradually thins into the ICM with a high incidence of breaks in the ICM that develops along the edge of the coloboma or toward the center.[36,37,38,39] Retinal tears within such abnormal tissues are difficult to identify by ophthalmoscopy because of the lack of the contrast of the fundus. Schubert[36] evaluated the histological section of 8 eyes with a coloboma-associated RDs that had both a central tear in the inner layer and a tear in the outer layer at the margin of the coloboma.

Studies of OCT images have shown that the RDs in colobomatous eyes were commonly caused by a tear in the ICM.[39] The ICM and the margin of coloboma were the important barriers against the development of RDs. The tears led to a connection between the space beneath the ICM and the subretinal space.[39]

Schubert[37] evaluated the clinical records and histologic sections of 14 children (ages 1 day to 17 months) and 7 adults (17–78 years) with a choroidal coloboma. In children, the extracolobomatous inner retinal layers extended centrally forming the ICM. Duplication of the outer retinal layers and a horizontal shift of Müller cells created a triangle and a locus minoris resistentiae adjacent to the laterally displaced RPE.[36,37] Part of the locus minoris resistentiae was an incomplete layer of photoreceptors excluding the Müller cells. In adults, an atrophy of the ICM was manifested as a central schisis, thinning of the neuroepithelium, and formation of a tear of the ICM. The atrophy was related to a decrease in the density of blood vessels within and beneath the ICM and the size of the coloboma. The margins of the colobomas had blood vessels, RPE hypertrophy, and choroidal and scleral thickening in a compact and intertwined arrangement. These pathological findings could explain the increased risk of RD with increasing age because of the glial atrophy, schisis, and hole formation in the ICM. The separation of the locus minoris resistentiae from the RPE which disrupted the barriers to fluid flow led to the rhegmatogenous RD. In addition, the process of developing the RD was expected to be worsened by scleral ectasia, increasing vitreous traction at the margins, and retinovascular ischemia within the ICM.

Tanaka et al.[40] evaluated the vitreoretinal structure at the margin of the choroidal coloboma in infants and older patients by swept-source OCT. The extra colobomatous central retina spread to the margin and continued as the marginal ICM. On the other hand, the outer layers of the marginal ICM were reversed and duplicated at the point of reversal.[37,38] The expected doubling was confirmed in all infant eyes, but in none of the older eyes whose outer layers of the marginal ICM were not clear.[40] However, at the border between the layered marginal ICM and monolayered central ICM, the point of reversal was detected between the marginal ICM and central ICM in all patients whose outer layers of the marginal ICM were clear. Further examinations of OCT images showed that the marginal ICM schisis and central ICM schisis were both present in eyes with a vitreous traction. However, the RDs in 4 eyes were not connected to the central ICM schisis but only to the marginal ICM schisis with a marginal ICM break in 1 eye. Swept-source OCT showed that the RPE hyperplasia adhered tightly to the retina, and that the glial triangle adhered tightly to the sclera. These attachments indicated the presence of three barriers including the remaining outer plexiform layer to the development of RDs after marginal ICM schisis. They concluded that swept-source OCT images showed the point of reversal in infant eyes and showed that the point of reversal could be identified in spite of the atrophic changes of the outer layer of the marginal ICM in the older eyes similar to the histopathological findings.[36,37]

The OCT findings suggested that the schisis of the marginal ICM and central ICM resulted from vitreous traction at the coloboma margins. Breaks in the ICM were observed both in the marginal and central ICM, and in cases of a central ICM break, a tightly adhering glial triangle prevented the progression of the RD toward the space of the sub-marginal ICM. Contrarily, vitreous fluid from the break in the marginal ICM passed through the outer plexiform layer into the subretinal space to form a RD only in the case when the fluid was not blocked by an RPE barrier. The recent advancement of OCT makes it easier to evaluate the pathologies of choroidal coloboma. However, the use of multiple imaging modalities would be valuable for assessing choroidal coloboma-related RD or just the choroidal coloboma [Figure 1].

Figure 1.

Fundus photographs of the left eye of a 26-year-old male with a choroidal coloboma at the initial visit. (a) Ultra-widefield image showing an asymptomatic localized retinal detachment connected to the edge of the choroidal coloboma (arrows). (b) Ultrasoundsonography showing excavated staphyloma (arrows) around the optic disc. (c) Fluorescein angiographic (FA) image at an early phase showing a diffuse hyperfluorescent lesion (arrows) at the edge of the coloboma corresponding to the localized retinal detachment. (d) FA image at a late phase showing a window defect at the hyperfluorescent lesion of the localized retinal detachment. The lesion of the coloboma has turned more hyperfluorescent. (e and f) Widefield optical coherence tomographic image showing a local retinal detachment (arrow) connected from the detachment of marginal intercalary membrane. The vitreous traction (arrowheads) is connected to the central intercalary membrane

Treatment

The repair of coloboma-associated RDs is a surgical challenge especially if the optic nerve is involved, and if there are associated ocular anomalies such as microphthalmia, cataract, or lens coloboma.[5,41,42] The surgical repair principles are the same for RDs in an eye where the RD does not involve the area of the coloboma. Wang and Hilton[43] reported the results of scleral buckling for coloboma-associated RDs [Table 1]. They placed the buckle at the margins of the coloboma with two radial buckles (as the Chinese Figure Eight, 八). A retinal reattachment was achieved in 7 of 14 eyes if the RD involved both edges of the coloboma. The length of the buckles was adjusted to the size of the coloboma. Patnaik and Kalsi[44] reported a successful reattachment in a patient in which a silicone sponge rod buckle was placed radially to extend from the disc to the ora after applying cryopexy. However, RDs due to a break within the coloboma has poor outcomes with scleral buckling, and vitrectomy is preferred.

Table 1.

Surgical procedures

	Eyes	Retinal breaks located within or margin of coloboma	Surgical procedures	Retinal reattachment (%)
Patnaik and Kalsi[44]	5	4	Diathermy or cryopexy +/scleral buckling	50
Wang and Hilton[43]	14	-	Two radial buckles	50
Hanneken et al.[53]	8	8	Vitrectomy, cyanoacrylate retinopexy (4 eyes)	87.5
Gopal et al.[41]	17	17	Vitrectomy, PC, cryopexy	81.8
McDonald et al.[49]	7	7	Vitrectomy, PC	100
Lee et al.[52]	1	1	Vitrectomy, perfluorocarbon liquid tamponade	100
Hotta et al.[54]	5	4	Vitrectomy, cyanoacrylate retinopexy (4 eyes)	100
Gopal et al.[42]	85	85	Vitrectomy, PC	81.2
Giansanti et al.[51]	1	1	Pneumatic retinopexy, PC	100
Wei et al.[48]	5	5	Vitrectomy, PC (diode laser), incision of ICM	100
Uhumwangho and Jalali[29]	90	-	Vitrectomy, encircling band, silicon oil tamponade	46.2
Abouammoh et al.[32]	119	70	Vitrectomy, PC, cryopexy (silicon oil tamponade 77.3%)	87.4
Kannan et al.[33]	31	8	Vitrectomy, PC, cryopexy (silicon oil tamponade 93.5%)	58.1
Hocaoglu et al.[34]	10	5	Vitrectomy, PC, silicon oil tamponade	90
Shenoy et al.[47]	148	-	Vitrectomy and silicon oil tamponade	88.5

PC=Photocoagulation, ICM=Intercalary membrane

Gopal et al.[42] reported the findings in 85 eyes of 81 patients with RDs related to a choroidal coloboma. The eyes underwent pars plana vitrectomy with internal tamponade with silicone oil (80 eyes) or perfluropropane gas (5 eyes). Endolaser photocoagulation was performed along the coloboma margins. A recurrence of the RD occurred in 16.3% of silicone-oil-filled eyes and 60% of gas-filled eyes. Silicone oil was removed in 80% of the eyes. After the silicone oil was removed, 15.6% of the eyes had a recurrence of the RD. After a mean follow-up period of 13.4 months, 81.2% of eyes had an attached retina, and the visual acuity had recovered equal to or better than 10/200 in 69.4% of eyes. A thorough removal of vitreous attachments and incision of the ICM to weaken it are important steps to relieve traction on the break within the ICM. Laser retinopexy can then be applied around the coloboma margins to create a border of chorioretinal adhesion. However, it is difficult to create chorioretinal adhesions around the causative holes within the ICM because the choroid and RPE are absent.

Abouammoh et al.[32] reported that anatomical success was achieved in 87.4% of 119 eyes that underwent vitrectomy with retinopexy of the edge of the coloboma and primary breaks. Anatomical success was significantly higher in eyes that had a long-lasting tamponade (P = 0.006). Cryotherapy was significantly associated with a failure of primary vitrectomy (P = 0.028). The placement of an encircling band did not affect the anatomical outcomes (P = 0.75). Most of the eyes (60%) with a recurrence of the RD after primary vitrectomy had a primary break in the unaffected retina. Uhumwangho and Jalali[29] reported that complications following RD surgery had occurred in 86.7% of the eyes. The most frequent change was a recurrence of the RD (53.8%). The optimal treatment of a RD in eyes with chorioretinal colobomas is pars plana vitrectomy with a long-acting tamponade such as silicone oil or octafluoropropane. Endotamponade with gas is preferred over silicone oil.[45] Gonvers[46] has pointed out the potential risk of silicone oil getting into the subretinal space through the colobomatous defect.

With the advent of small gauge pars plana vitrectomy, most coloboma-related RDs are now repaired by an intraocular approach [Figure 2].[33,34,47] The identification of the breaks in the ICM is easier with intraocular viewing during pars plana vitrectomy.[30,42] The advantages of small-gauge vitrectomy may be due to the reliable creation of a posterior vitreous detachment by small instruments, and the use of intravitreal injection of triamcinolone acetonide to make the vitreous cortex more visible.

Figure 2.

Fundus photographs of the same patient visited 1 year after the initial visit due to acute visual disturbance by an extended retinal detachment associated with a choroidal coloboma. (a) Ultra-widefield image showing the retinal detachment connected to the edge of the choroidal coloboma (arrows). (b) Fundus autofluorescent image showing a dark area corresponding to a retinal detachment (arrows). (c) Optical coherence tomographic (OCT) image showing that the retinal detachment is connected to the choroidal coloboma. The inner retina within the coloboma is connected to an intercalary membrane (ICM). (d) Ultrawide-angle image showing a complete retinal reattachment from the edge of the choroidal coloboma by endolaser scars (arrowheads). Laser photocoagulation was also performed around the iatrogenic break (arrow). (e) Fluorescein autofluorescence image showing the absence of the dark area corresponding to the retinal reattachment. Laser scars can be seen at the edge of the coloboma (arrowheads) and the iatrogenic break. (f) OCT image showing that the retinal detachment was disconnected by the laser scars (arrowheads) and persistent fluid beneath the ICM (arrow) at the choroidal coloboma

Wei and Chen[48] reported on 5 eyes with a RD resulting from a choroidal coloboma involving the disk that underwent vitrectomy with incision of the entire ICM along the margin of the coloboma. Part of the ICM in the macular region remained, and together with the macular retina was displaced slightly to healthy RPE. Then, titrated diode laser burns were applied to the functional border of the disk (border of the papillomacular bundle) to reduce the nerve fiber layer damage. The retina was reattached in all eyes, but the visual improvement was limited.

In eyes where the coloboma involves the optic disc, peripapillary endolaser photocoagulation through the papillomacular bundle may result in laser-induced retinal nerve fiber layer damage. This would then lead to a poor improvement of the vision and visual field defects even with the retina reattached. McDonald et al.[49] reported on the results of vitreous surgery with air-fluid exchange and endodrainage through preexisting retinal breaks. This surgery was done on seven eyes with RDs caused by retinal breaks at the margin or within the choroidal coloboma. Part or all of the rim of the choroidal coloboma in 6 eyes had endophotocoagulation. Two eyes that did not have a postoperative visual improvement underwent intraoperative endolaser treatment over 360° around the optic nerve. If peripapillary endophotocoagulation was performed, especially through the papillomacular bundle, nerve fiber damage may occur and prevent recovery of vision, despite the retinal reattachment. A longer-wavelength laser may be recommended. Corcostegui et al.[50] used argon laser endophotocoagulation of the retinal breaks, but when the coloboma involved the optic disc, red krypton endophotocoagulation was used. Wei and Chen[48] used diode laser to reduce nerve fiber damage.

Giansanti et al.[51] reported a reattachment of a retinal break after pneumatic retinopexy followed by laser coagulation around the margin of the choroidal coloboma. A choroidal coloboma is usually located inferiorly, and most of the retinal breaks are detected within the coloboma. Thus, pneunmatic retinopexy may not be used for these cases. Lee et al.[52] described a case of recurrent RD associated with a choroidal coloboma following vitreous surgery with sulfur hexafluoride gas. This eye was successfully repaired by using liquid perfluorocarbon, perfluoroperhydrophenanthrene (Vitreon) as a short-term tamponade and endolaser photocoagulation.

Hanneken et al.[53] used vitrectomy on eight eyes with a complicated RD associated with a choroidal coloboma with no evidence of peripheral retinal breaks. Atrophic breaks were detected in 5 eyes within the coloboma and in 4 eyes at the margin of the coloboma. Adjunctive surgical techniques were necessary with cyanoacrylate retinopexty in four eyes, silicone oil tamponade in 5 eyes, and retinetomy in 2 eyes. Hotta et al.[54] described vitrectomy and direct closure of the breaks with cyanoacrylate glue without silicone oil tamponade or endophotocoagulation around the disc or at the site of the papillomacular bundle. Retinal breaks were identified at the margin of or within the coloboma, and cyanoacrylate glue was applied to the retinal breaks in 4 of 5 eyes and the suspected retinal break in one eye. The retina was successfully reattached in all eyes by vitrectomy and cyanoacrylate retinopexy [Figure 3]. However, direct closure was not achieved in most cases and cyanoacrylate glue was not effective in a split or atrophied ICM. Only, the inner layers of the schisis were sealed, and the progression of the atrophy can enlarge the hole as the ICM contracts.

Figure 3.

A 34-year-old woman with a retinal detachment associated with choroidal coloboma with cyanoacrylate retinopexy. (a) Fundus image was taken in 2004 after vitrectomy with cyanoacrylate retinopexy. The cyanoacrylate glue (arrowheads) was applied at the inferior quadrants of choroidal coloboma. (b) Fundus image taken in 2024 after a vitrectomy with cyanoacrylate retinopexy (arrowheads). The cyanoacrylate glue has persisted at the same position for 20 years. (c) Magnified fundus image. Cyanoacrylate glue (arrowheads) was applied to the inferior quadrants of the choroidal coloboma. (d) Ultra-widefield image showing that the retina is reattached after more than 20 years

The current approach, therefore, would be to isolate the coloboma from the vitreous traction by vitrectomy and create chorioretinal adhesions around the coloboma margin by laser coagulation.[41,42,43,44,45,46,47,48,49,50] In eyes with a chronic macular hole, the use of an amniotic membrane graft has been reported to be successful in closing the macular hole.[55,56,57,58,59,60,61] An amniotic membrane plug has been used for RDs associated with the morning glory syndrome[62] and optic disc pit maculopathy.[63] Vitrectomy and the amniotic membrane plug in the causative breaks within the coloboma may be an ideal treatment for retinal detachment associated with a choroidal coloboma by reducing laser-induced nerve fiber damage.

Uhumwangho and Jalali[29] reported that the incidence of RD was 2.9% in eyes that received prophylactic laser photocoagulation, whereas the risk of RD was 24.1% in eyes left untreated. Prophylactic laser retinopexy to the border of choroidal coloboma appears to be a good option for reducing the risk of coloboma-related RDs.[64] However, in the majority of the eyes, the optic disc located within the choroidal coloboma making it difficult to safely use a complete treatment.

Conclusions

RDs are occasionally associated with choroidal colobomas. Histologically, the area of the choroidal coloboma lacks the normal choroid, RPE, and retina. Near the margins of the coloboma, the inner retinal layer has a central continuation of the marginal ICM within the coloboma. The outer layer folds back, becomes disorganized, and fuses with the RPE. The inner retina gradually thins into the marginal and central ICM, and there is a high chance of tears in the marginal ICM developing along the edge of the coloboma or toward the center. Because of the high association of the causative retinal breaks being located within the colobomatous area, vitrectomy, endolaser around the margin of coloboma, and long-term tamponade including silicone oil or gas is recommended. Macular involvement within the area of laser treatment should be avoided. However, the recurrence rate will still be high. Further treatment to reduce laser-induced nerve fiber damage including the use of amniotic membrane and inverted internal limiting membrane should be mandatory.

Conflicts of interest

The author declares that there are no conflicts of interests of this paper.

Funding Statement

Nil.