Opacification of hydrophilic intraocular lenses associated with vitrectomy and injection of intraocular gas

Introduction

Opacification of hydrophilic acrylic intraocular lenses (IOLs) following intraocular gas injection has been described with numerous IOL models.1–9 In most reports, the opacification occurred following intracameral injection of air, sulfur hexafluoride (SF6) or perfluoropropane (PFP) during Descemet’s stripping endothelial keratoplasty (DSAEK), Descemet’s membrane endothelial keratoplasty (DMEK) or intracameral gas injection for treatment of Descemet’s membrane detachment following cataract surgery.1–7 In several reports, the opacification occurred after vitrectomy with intravitreal gas injection. In all these cases, the opacification appeared almost exclusively on the anterior surface of the IOL although the gas was injected into the vitreous.6 8–10 The typical appearance in most cases is surface irregularity confined to the central part of the optic, which corresponds to the opening of the pupil or the anterior capsulorhexis.6 8–10 Laboratory analysis with scanning electron microscope (SEM) using energy dispersive x-ray spectroscopy (EDX) or staining with alizarin red and von Kossa stains demonstrates deposition of calcium (Ca) on IOL surfaces.6 8–10

Here we present a series of 11 hydrophilic acrylic IOLs from several manufacturers that opacified after injection of intravitreal gas during vitrectomy. This series is important in light of the rising number of PPV surgeries performed in recent years, especially in the elderly population.11 Therefore, we anticipate a rising incidence of hydrophilic acrylic IOL opacifications in the future, hence the importance of retinal surgeons’ awareness and recognition of this complication.

Materials and methods

Eleven cases of hydrophilic IOLs that opacified following PPV with intravitreal gas injection are described. Eight explanted IOLs were sent for analysis by the surgeon to the Department of Ophthalmology, Kaplan Medical Center, Rehovot, Israel, and the David Apple International Laboratory for Ocular Pathology, Department of Ophthalmology, University of Heidelberg, Germany. The explanted IOLs were analysed by light microscopy and SEM. IOLs were stained for calcium with 1.0% alizarin red and von Kossa stains. Elemental analysis by EDX was performed. SEM was performed by Zeiss Supra 55 or Zeiss Ultra 55 microscopes at the Weizmann Institute of Science, Rehovot, Israel, or at the Max Planck Institute for Polymer Research, Mainz, Germany. Three IOLs were not explanted. The surgeons attached information about the IOLs, patients and surgical procedures. The study proposal was reviewed by the chairperson of the ethics committee at the Kaplan Medical Center, Rehovot, which confirmed that ethics committee approval was not required.

Results

The characteristics of the 11 cases and the surgical settings are depicted in tables 1 and 2. Seven patients were women and four were men. The mean age at IOL implantation was 63.2 years (range: 50–76 years). The IOLs were implanted between June 2003 and October 2016. Six patients (cases 1, 2, 4, 5, 6 and 7) underwent primarily phacoemulsification with IOL implantation. Five of these surgeries were uneventful. In one patient (case 2), anterior vitrectomy was performed, and the IOL was implanted in the sulcus. In six patients with prior IOL implantation, PPV with intravitreal gas injection was performed 3 months–6 years after cataract surgery. At the time of PPV, the IOLs were clear. The other five patients (cases 3, 8, 9, 10 and 11) underwent simultaneous phacoemulsification with IOL implantation and PPV with intravitreal gas injection. Three patients underwent two PPV surgeries (cases 3, 5 and 9). In one of them (patient 5) PPV was performed before phacoemulsification and IOL implantation, and in another patient (9) the IOL opacified after the first PPV. In cases 1, 2, 3 and 7, the gas fully expanded in the posterior chamber postoperatively, but this was not mentioned in medical files of other cases. Elevated postoperative intraocular pressure (IOP) was observed in three patients (1,2 and 7). Elevated IOP was not mentioned in the operative notes that were available or in patient charts before IOL explantation.

General diseases, prior ocular history and best-corrected visual acuity (BCVA) before and after IOL explantation are described in online supplementary table 1. Part of the data was not provided by the surgeons. Two of the patients had diabetes, five had hypertension and one suffered from asthma. Before explantation, BCVA ranged from light perception to 6/15. After IOL exchange BCVA improved in three patients to 6/10 (cases 1, 6 and 7) and in one patient with poor macular function it improved from light perception to 6/60 (case 3). In one eye BCVA remained counting fingers due to macular atrophy (case 2) and in one patient it worsened from 6/21 to 6/30 (case 8).

The IOLs were produced by six manufacturers (table 2). Opacification of the IOL was first noted 1 month–6 years after PPV during regular clinic visits. In eight patients, the IOLs were explanted between July 2013 and July 2015. The explantation was performed 1 month–9 years after opacification was first noted. During this period, the opacity became denser and obscured vision. One IOL was explanted with the capsular bag (case 5). In three patients, the opacified IOL was not explanted: two of them (cases 9 and 10) had poor visual potential; the third patient (case 11) experienced glare and blurred vision. However, her visual acuity was 6/12, and she rejected IOL explantation. IOL opacification occurred mainly on the anterior aspect, forming a round rough surface that corresponded to the pupillary entrance or the capsulorhexis margin.(figures 1A, B, 2A, B, C, 3C). In the sulcus implanted IOL (case 2), the opacification extended over the entire optic area as well as part of the haptics (figure 4A, B, C). In one patient (case 3), prominent opacification occurred also on the posterior surface of the IOL(figure 5A, D). This patient was treated previously by pan-retinal laser photocoagulation for proliferative diabetic retinopathy (PDR) and triamcinolone intravitreal injections for macular oedema. He underwent PPV twice: the first PPV combined with phacoemulsification was performed for ERM with SF6 injection. After 4 months, the patient developed RD and underwent a second PPV with PFP injection (fully expanded gas bubble postoperatively). IOL opacification was first noted 11 months after the second operation. The IOL was explanted 8 years later due to inability to examine the fundus for diabetic retinopathy follow-up. Neodymium-doped yttrium aluminium garnet capsulotomy before PPV was performed only in one patient (case 2) that underwent anterior vitrectomy during cataract surgery with vitreous loss.

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Laboratory examination by light microscopy demonstrated granular deposits on the IOL surface that stained positive for Ca by alizarin red and von Kossa method(figure 2A, B). SEM showed granular deposits on the surface of the IOL in different patterns (figures 1, 4 and 5). EDX demonstrated that the granules consisted of Ca and phosphorus (P) (figures 2D, 4, 5D). The granules were present on and below the anterior surface of the IOLs.

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Discussion

Opacification of hydrophilic acrylic IOLs following intracameral injection of air has been reported following endothelial keratoplasty (DSAEK and DMEK)1–4 7 or Descemet’s membrane detachment repair.5 The opacified area matched the pupillary or capsulorhexis opening at the anterior surface of the IOL.1–7 Laboratory analysis by histochemical staining, SEM and EDX of explanted opacified IOLs detected deposition of Ca and P on the anterior surface and subsurface.1–7 The exact mechanism of calcification of the exposed IOL surface is under investigation. A hypothesis of local damage to the hydrophilic IOL surface due to the direct contact with air/gas at the exposed area has been suggested. This damage may lead to Ca/P deposition from the aqueous humour.2 3 6 In their information for users (IFUs), hydrophilic IOL manufacturers alert against IOL dehydration.12 13 In the Medicontur IFU, it is stated that a hydrophilic IOL that was kept in open air for longer than 1 min should be discarded.12 However, a similar pattern of hydrophilic IOL calcification has been observed when gas was injected to the vitreous during PPV surgery.8–10 Werner et al 2 suggested that leakage of gas to the anterior chamber may explain the same observation. This explanation is supported by the findings in our 10th patient. In this patient, the gas migrated to the anterior chamber 1 day postoperatively. Drying of the anterior surface of the IOL was noted (figure 3A). Following gas disappearance, the IOL looked transparent on the 1-month follow-up visit (figure 3B). Examination 8 months postoperatively detected deposits on the anterior IOL surface at the pupillary entrance (figure 3C). However, in many reported cases, the presence of gas in the anterior chamber was not mentioned.6 8–10 In these cases, the mechanism of opacification may be different. We hypothesise that filling of the vitreous cavity with slowly dissolving gas for a long period may relatively dehydrate the IOL despite intact posterior capsule. IOL dehydration may occur during sleep or while patient is supine, even in partially filled vitreous cavity, due to direct contact between gas and IOL. The dehydration may induce chemical alterations on the IOL surface. Later, Ca/P from the aqueous humour is deposited in the exposed areas. Our cases support this hypothesis. In 9 out of our 11 cases of in-the-bag IOLs (cases 1, 4–11; table 1), the affected area is the anterior central part of the optic at the pupillary or capsulorhexis opening with sparing of the covered areas of the IOL (figure 1A, B, (figure 2A,B, C), (figure 3C). In case 2, Ca/P deposits were present all over the anterior optic and haptics (figure 4A, B, C), because the IOL was implanted in the sulcus and therefore not covered by the capsule anteriorly. This observation may indicate that the contact with the aqueous humour is responsible for the deposition of the Ca/P on the exposed IOL surface. In one patient (case 3), prominent opacification occurred also on the posterior surface of the IOL (figure 5A, B, C, D). This is the first report of Ca/P deposition on the posterior IOL surface after intraocular gas injection. The patient had PDR and underwent PPV twice, 4 months apart, with fully expanded gas bubble in the posterior chamber after the second PPV. The deposition of Ca/P in this patient on the posterior IOL surface (figure 5C, D) could result from the disruption of the blood–retinal barrier that occurs in PDR. A study on Ca and P levels in the aqueous humour of eyes of patients with diabetes found increased P levels compared with non-PDR or otherwise healthy patients. Ca levels did not differ between the groups.14 Elevated aqueous P levels may explain the extensive IOL Ca/P sedimentation that occurred in this patient. The reason why certain eyes develop IOL deposits is uncertain. In DSAEK surgery, a correlation to repeated air/gas injections has been described.2 3 In cases 1, 2 and 7, fully expanded gas bubble in the posterior chamber with subsequent elevated IOP was detected postoperatively, and partial gas removal was performed in two cases. Elevated IOP was not reported in the available operative notes. When inflating the eye totally with gas, there is no fluid meniscus that may prevent the IOL from drying leading to surface modifications that promote sedimentation of Ca/P. Different morphological patterns of Ca/P deposits (volcano, target and knob-like elevations) have been demonstrated.6 9 These sediments may extend deeper into the body of the IOL or consist of subsurface calcifications that are breaking through to the surface.3 6 9 The variability of different patterns may be attributed to the interaction of the various hydrophilic IOLs that may differ in their material composition. In this series, we report for the first time the opacification of Hanita B lens, Hanita C lens, Xcellence Idea, Biotech vision care Eyecryl and U.S. optics SL-902 IOLs following intraocular air or gas injection.

PPV has become the preferred surgical procedure for RD in patients with pseudophakia.11 15–17 Other indications such as ERM peeling and macular hole surgery increased the number of PPV performed annually.11 Patients over 65 years of age were found to have the highest rates of vitrectomy.11 Some of these patients may be pseudophakic before PPV surgery, and in many, a combined phacoemulsification and PPV is performed due to existing cataract.11 We analysed the operative notes and patient charts at Kaplan Medical Centrerduring 7 years from 2009 to 2015 (unpublished data). There were 166 PPVs with intravitreal gas injection with hydrophilic IOLs. The incidence of IOL opacification was 7%. In four patients, the IOLs were explanted, and on eight additional IOLs, opacification was documented. Two out of these 12 patients have diabetes. The numbers are too small to determine if diabetes was a risk factor.

Manufactures of hydrophilic IOLs alert in their IFU against IOL dehydration.12 13 We can hypothesise that the greater the occupancy of posterior chamber gas (%), the greater the chance of IOL dehydration and subsequent opacification. In ERM or macular hole surgery, at the conclusion of the vitrectomy, a partial (rather than full) gas bubble and a non-expandable gas composition may be preferred to allow fluid meniscus adjacent to the IOL preventing the IOL from drying. The patient may be instructed to sleep face down, to diminish contact between the gas and the IOL similar to phakic patients undergoing PPV with gas injection. In RD surgery, which is sight threatening, the immediate goal is reattachment of the retina and gas application and head position is derived from the clinical condition. The prevalence of surface opacification of IOLs may be underdiagnosed since it can allow reasonable vision. In a series of five opacified IOLs after DSAEK, only one IOL was exchanged due to decrease in vision.3 However, optical bench analysis of explanted opacified IOLs following endothelial keratoplasty demonstrated deterioration of the optical quality.7 Due to gradual decrease in the optical clarity of the opacified IOLs, the interval between the beginning of opacification to the actual explantation may last between months to years.2 In three of our patients, IOL exchange improved BCVA to 6/10 (cases 1, 6 and 7). In other cases, vision remained poor due to macular dysfunction. In our 11th patient, the sedimentation on the IOL surface was not homogenous, leaving a relatively clear central zone still allowing a 6/12 vision. The patient experienced glare but refused IOL explantation.

In conclusion, injected intravitreal gas during PPV may cause opacification of hydrophilic IOLs due to surface Ca/P sedimentation. Due to the rise in PPV procedures performed annually,11 the incidence of IOL opacification following this procedure is expected to increase. A significant percentage of patients may be pseudophakic at the time of surgery with a hydrophilic acrylic IOL already implanted. It is important to alert these patients about the possible IOL opacification following PPV. When performing simultaneous PPV with phacoemulsification, a hydrophobic acrylic IOL may be preferred.