Study on the effectiveness and safety of Foldable Capsular Vitreous Body implantation.

BACKGROUND: Foldable capsular vitreous body (FCVB) was designed to treat severe retinal detachment. The aim of this study was to evaluate the efficacy and safety of the implantation of foldable capsular vitreous body in 1-year follow-up.
METHODS: A retrospective analysis was conducted for 20 patients with severe ocular trauma or silicone oil (SO) dependent eyes underwent vitrectomy and FCVB implantation in a 1-year follow-up. All treated eyes were peformed clinical examinations involved the visual acuity (VA) examination, Goldmann applanation tonometer, noncontact specular microscopy, fundus photography, B-Scan examination and optical coherence tomography (OCT). The groups were compared with t-test and the McNemar - Bowker test.
RESULTS: In 1-year follow-up, 20 eyes were evaluated in the study. FCVB well supported the vitreous retina in all treated eyes, and 6 treated eyes achieved retinal reattachment 12 months after FCVB implantation. There were no significant differences in VA before and after FCVB implantation (P = 1.000). In addition, the postoperative IOP markedly elevated from the preoperative IOP of 12.90 ± 7.06 mmHg to 15.15 ± 3.36 mmHg (P = 0.000017). The intraocular pressure (IOP) of 10 eyes maintained at a normal level after surgeries. The other 10 eyes showed slightly lower IOP within the acceptable level. Though two patients developed keratopathy and ocular inflammation respectively, other treated eyes were symmetric with fellow eyes showing satisfactory appearance. Moreover, there was no SO emulsification or leakage happened in the observation.
CONCLUSIONS: FCVB implantation was an effective and safe treatment in the eyes with severe retinal detachment.

Background

Over 80% of the structure of the eyeball is natural vitreous body, which contains only 1% of proteins, hyaluronan, lipids and inorganic chemical compounds. Natural vitreous body, which was proved to maintain a certain spatial relationship with dipolar water molecules, has the ability to support the retina, supply nutrition, stabilize intraocular metabolism, act as cell barrier and ocular refractive media, etc [1] However, the composition of natural vitreous body is unclear, which means it is impossible to create artificial vitreous body [2-4]. Furthermore, due to the natural vitreous body is non-renewable [5-7], vitrectomy and SO tamponade are required when vitreoretinal diseases occur, such as retinal detachment caused by severe ocular trauma, post-trauma proliferative vitreoretinopathy, proliferative diabetic retinopathy and endophthalmitis [8-11]. SO is a kind of the vitreous substitutes which also include gases, heavy water, heavy SO. And Vitreous tamponade aims to replace the natural vitreous body with vitreous substitutes to support the retina, promote the anatomical reduction of the retina and prevent the eyeball from shrinking [5, 12]. But current discovered vitreous substitutes have short-term life-span and high toxicity causing severe complications in the eyes [13, 14]. Specially, SO has been proved to be toxic for ciliary body and attribute to emulsificate in the eyeball, though SO has the most stable physical and chemical attributions among all the vitreous substitutes [15]. Researchers have been working hard to find suitable vitreous substitutes in the past decades before the invention of FCVB [12, 16].

FCVB is an innovative product initially developed independently by China [17]. It was designed to refine the way that SO work in the inner cavity of eyeball, and help to support the retina. Since FCVB has excellent mechanical strength, refractivity and biocompatibility, it is able to prevent SO from displacement and emulsification [18]. Moreover, the post-surgical complications are effectively reduced [19]. Unlike SO tamponade, there is no more need for patients to keep prone positions after surgeries [20].

FCVB have been approved in vitro and animal experiments [21-23]. Nevertheless, the clinical safety and efficacy of FCVB have not been verified yet, and previous associated clinical studies were not enough [18, 19, 24, 25]. In this study, FCVB implantation, as a new method treating severe ocular trauma or SO-dependent eyes, was performed on 20 patients with retinal detachment. It aimed to study the clinical safety and efficacy of FCVB for the patients.

Methods

Study design

A retrospective study of 20 cases involving 20 patients with FCVB implantation was conducted between September 2017 and September 2018. The basic demographic information of the patients is shown in Table 1. The average age was 40.05 years old (2–65 years old), including 17 males and 3 females. There were 13 cases of eyeball rupture, 5 cases of SO dependent eyes, one case of endophthalmitis, and one case of eyeball atrophy. The study protocol was reviewed and approved by Medical Ethics Committee of the People’s Liberation Army’s 988rd Central Hospital (2017006). The clinical trials strictly adhered to the principles of The World Medical Association Declaration of Helsinki and have been successfully registered.

Table 1

Preoperative general information and eye diagnosis information of patients

Patient	Sex	Diagnosis		Initial VA (logMar)	InitialIOP (mmHg)	The time from diagnosis to operation (days)	FinalVA (logMar)	Final IOP (mmHg)	Surgical sucess (yes/no)	Follow-up time (months)
		Main diagnosis	other ophthalmological diagnosis
01	male	1. ocular rupture; 2. vitreous hemorrhage	1.irideremia; 2.lack of lens	NLP	Tn-2	4	NLP	Tn	yes	12
02	male	1. retinal detachment	1. vitreous hemorrhage; 2. anterior chamber hemorrhage;3. irideremia; 4. lack of lens	NLP	Tn + 2	3	LP	Tn-1	yes	12
03	male	1. ocular rupture; 2. retinal detachment	1. eyelid trauma	NLP	Tn-2	8	NLP	Tn	yes	12
04	female	1 ocular rupture; 2. retinal detachment	1. irideremia; 2. lack of lens	NLP	Tn-1	28	LP	Tn	yes	12
05	male	1. ocular rupture; 2. retinal detachment	1. iridodialysis	NLP	Tn-1	9	NLP	Tn	yes	12
06	male	1. ocular atrophy after SO tamponade	1. endophthalmitis; 2. corneal degeneration; 3. lack of lens	NLP	Tn-1	16	NLP	Tn	yes	12
07	male	1. retinal detachment; 2. silicone oil dependent eye	1. optic atrophy; 2. irideremia; 3. lack of lens	HM	Tn-1	15	HM	Tn	yes	12
08	male	1. ocular atrophy	1. exotropia; cataract; 2. lens dislocation	NLP	Tn-1	6	NLP	Tn	yes	12
09	male	1. ocular rupture; 2. retinal detachment;3. chorioretinal detachment	1. ocular rupture	HM	Tn-1	4	HM	Tn-1	yes	12
10	male	1. recurrent retinal detachment; 2. ocular atrophy	1. lack of lens	FC/30 cm	Tn-1	2	HM	Tn-1	yes	12
11	male	1. recurrent retinal detachment	1. lack of lens; 2. secondary glaucoma	HM	Tn + 1	2	LP	Tn-1	yes	12
12	female	1. retinal detachment	1. intraocular lens implantation; 2. exotropia; 3. vitreous opacities	NLP	Tn-1	5	NLP	Tn	yes	12
13	male	1. ocular rupture		LP	Tn	14	LP	Tn-1	yes	12
14	male	1. ocular rupture; retinal detachment; 2. choroidal detachment	1. vitreous hemorrhage	NLP	Tn-1	14	NLP	Tn	yes	12
15	male	1. retinal detachment; 2. ocular atrophy	1. traumatic cataract, 2. vitreous opacity, exotropia	NLP	Tn-1	2	NLP	Tn-1	yes	12
16	male	1. SO dependent eye	1. high myopia;2. corneal degeneration	LP	Tn-1	6	LP	Tn-2	yes	12
17	male	1. recurrent retinal detachment;2. intraocular lens implantation	1. irideremia; 2. lack of lens	HM	Tn-1	4	LP	Tn-2	yes	12
18	female	1. ocular rupture; 2. retinal detachment	1. irideremia; 2. lack of lens	LP	Tn-1	0	HM	Tn-1	yes	12
19	male	1. ocular rupture; 2. retinal detachment		LP	Tn-2	20	LP	Tn	yes	12
20	male	1. ocular rupture; 2. retinal detachment	1. anterior chamber hemorrhage; 2. vitreous hemorrhage	NLP	Tn-1	6	NLP	Tn-1	yes	12

The age - ranges of patients: 2–65 years. Visual acuity (VA): NLP – No light perception; LP – Light perception; HM – Hand move; FC – Finger count. Intraocular pressure (IOP): Tn-2, 5–9 mmHg; Tn-1, 10–14 mmHg; Tn, 15–20 mmHg; Tn + 1, 25–34 mmHg; Tn + 2, 35–50 mmHg

Inclusion criteria

Patients with a severe retinal detachment that could not be cured with SO tamponade, such as posterior scleral ruptures with large disruptions of the retina or severe scleral ruptures with retinal detachments and choroidal damage, or they had to have rigid retinal re-detachments or inferior holes that occurred after more than 3 months of SO tamponade. In addition, the treated eyes should below PVR-B, its axial length ≤ 26 mm. A third-party committee of ophthalmologists should confirm that the detached retina could not be reattached with SO tamponade and satisfied the requirements of FCVB implantation.

If the retinal detachment could be treated with SO tamponade, the surgeon could stop the procedure and deny FCVB implantation.

Excluded criteria

The exclusion criteria were contraindications approved by the China Food and Drug Administration (CFDA). Excluded criteria were scar physique, glaucoma, eye inflammation, macular diseases and other diseases that the patients were deemed unsuitable for FCVB implantation. Adverse events should be recorded, such as unbearable foreign body sensations, uncontrollable bleeding, severe inflammation, endophthalmitis, severe disturbance of eye movement, diplopia and sympathetic ophthalmia during the study.

Surgical technique

After Inclusion, 20 patients (20 eyes) underwent FCVB implantation. The operating procedures consist of 9 steps: (1) Sterilization and retrobulbar anesthesia was performed before operation. (2) A three-ports vitrectomy was conducted to remove the intraocular lesion tissue of the retina and hemorrhage. (3) After conducting paracentesis of the anterior chamber, a 3.5 mm incision was create on the sclera as FCVB implantation site at either the 4 or 8 o’clock position 4.5 mm away from the corneal limbus. Perform gas-fluid exchange to lift the IOP over 50 mmHg and evaluate the state of retina with fundus observation. (4) The air tightness of FCVB was tested under ddH2O. (5) FCVB was properly fold and implanted into the cavity of eyeball through the incision with push injector. The lens surface of the capsule of FCVB should be placed facing the lens. If there is tilting, with iris repositor, the position of FCVB capsule can be adjusted properly. (6) The incisions were sutured carefully with an 8–0 absorbable suture. Then the SO was slowly injected into the capsule through the drainage valve with syringe until the IOP is approximately 15 mmHg. The injected SO volume, which should be less than the maximum injection volume of each model, was recorded. (7) The anterior chamber was fulfilled with adequate volume of viscoelastic. (8) Postoperative observation (capsule’s expansion, air bubble and the blood supply of retina in the capsule) to the end of the drain tube by connecting to the optical fibers. (9) The drain tube was ligated with the 5–0 non-absorbable suture and affix it to the sclera.

Postoperative medications: Methylprednisolone 80 mg intravenous drip for three days, then prednisone 70 mg, 10 mg per week reduction. If for the aged with systemic diseases, such medication should be used cautiously.

Follow-up examinations

Ocular examinations were performed at baseline, 1, 2, 3, 6 and 12 months after FCVB implantation. The arrangements of ocular examinations consist of VA with Snellen eye charts (transformed to logMAR) and IOP with Goldmann applanation tonometry (GAT; Haag-Streit AG, Köniz, Switzerlan), traditional slit lamp biomicroscopy (Nikon FS-2, Nikon Inc., Melville, NY), direct ophthalmoscopy, and fundus photography (TRC- 50EX; Topcon, Tokyo, Japan). A-scan ultrasound (CineScan A/B; Quantel Medical, Bozeman, MT), B-scan ultrasound (CineScan A/B; Quantel Medical, Bozeman, MT), noncontact specular microscopy (SP-3000P; Topcon, Tokyo, Japan), optical coherence tomography (OCT, Visante; Carl Zeiss Meditec, Dublin, CA), ultrasound biomicroscopy (UBM, SW-3200 Kinscan; Suoer, Tianjin, China) and were performed at baseline and 3 months after implantation.

Outcome measures

The primary outcome measure was the rate of complete retinal reattachment detected by B-scan ultrasound after the FCVB implantation. If conditional, OCT was also conducted.

The secondary outcome measure included VA, IOP, and axial length, as determined by the Snellen chart, Goldmann applanation tonometry, and A-scan, respectively. Classification of VA follows the typical scoring system: no light perception represented 0; light perception represented 1; hand motion represented 2; finger the perception represented 3; ≥0.05 acuity represented 4; and ≥ 0.1 acuity represented 5. The preoperative VA before FCVB implantation were at relative low level, representing less than 2.

All outcomes derived from photograph were determined by independent grading of retinal photographs, performed by the third-party Fundus Photograph Reading committee which consisted of ophthalmologists.

Statistical analysis

In this study, SPSS 15.0 (SPSS Inc., Chicago, IL, USA) was used for data analyses. IOP are expressed as Mean ± SD. A paired-samples test was used for comparison of IOP between baseline and 6 months after surgery. Analysis of categorical data followed by the McNemar - Bowker test was used to analyze between-group differences of VA, as well as IOP, and Fisher’s exact test was used when expected cell counts were below five. A two-tailed value of P < 0.05 was considered statistically significant.

Baseline information

Twenty patients (20 eyes) were enrolled in the study between September 2017 and September 2018. The demographic and ocular condition of patients at baseline examination are shown in Table 1. The mean age of the patients was 40.05 ± 20.66 years, and 85% of patients were male. Case 9 and Case 12 had severe ocular rupture with retinal and choroidal detachments. All the patients suffered severe ocular trauma or silicone oil dependent eye. Since that, the patients were performed vitrectomy and FCVB implantation. Also, all the patients had signed informed consent forms.

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