Cataract and diabetes: review of the literature

Advanced preoperative assessment and modern surgical techniques have significantly enhanced cataract surgery results for diabetic patients.

Abstract

Cataracts can cause visual impairment in diabetic patients. Diabetes mellitus affects different parts of the eye and causes many complications and problems before, during, and after intraocular surgeries. In this review, we will discuss the effects of diabetes on different aspects of cataract surgery and review the current management of diabetic cataracts. Careful preoperative examination of the patient's ocular surface, cornea, iris, and posterior segment, as well as the use of advanced phacoemulsification techniques, new intraocular lenses and the appropriate use of auxiliary medications such as nonsteroidal anti-inflammatory drugs and anti-vascular endothelial growth factors have improved the outcomes of cataract surgery in diabetic patients.

It is estimated that more than half a billion people between the ages of 20 and 79 worldwide have diabetes (10.5% of all adults in this age group). By 2030, that number will rise to 643 million.¹ Diabetes is associated with a 2- to 5-fold increase in cataracts.²

Cataract surgery for diabetic patients differs in many ways from nondiabetics. The conditions that affect different parts of the diabetic eye, such as ocular surface problems, corneal changes, glaucoma, macular edema, and retinopathy, increase the likelihood of surgical complications or postoperative visual impairment.

In 2008, we published a review article on the diabetic cataract and its related complications.³ Considering the importance of the subject and the advances that have been made in diagnostic and treatment methods in this field, we decided to perform an updated review of studies available in the literature.

METHODS

We performed an electronic search of human-based studies in PubMed, Scopus, and Google Scholar from January 1, 2010, until January 1, 2022, published in English, using “Cataract” and “Diabetes” as the keyword. We did not apply any restrictions on sex, age, and journal or article type. All references in included studies, as well as relevant systematic reviews, were manually searched for additional studies.

PART I: DIABETES MELLITUS EFFECTS ON DIFFERENT PARTS OF THE EYE

Ocular Surface and Dry Eye

Diabetic eyes are at increased risk of meibomian gland dysfunction, blepharitis, dry eye, superficial punctate keratitis, recurrent corneal erosion, persistent epithelial defects, susceptibility to injury, and ulcerations, which have been shown to be related to the duration of the diabetes, greater glycated hemoglobin A1c (HbA1c) levels, and the severity of diabetic retinopathy (DR).^4–8 Recently growing prevalence of diabetes mellitus (DM)–associated dry eye syndrome has been reported.⁹ Multiple mechanisms are described for diabetic corneal neuropathy including oxidative stress, hyperglycemia-mediated inflammation, and signal pathways (eg, P-neurokinin 1 receptor or epidermal growth factor receptor signal pathway).^10,11 In vivo confocal microscopy of diabetic corneas revealed reduced subbasal nerve density, reduced nerve branching, increased nerve tortuosity, and pronounced thickening of the nerves.^5,10 Moreover, lower corneal nerve fiber density was associated with higher HbA1c.¹² In some patients, combined trauma to epithelial cells, reduced corneal sensation, and delayed wound healing may cause or worsen diabetic keratopathy after ocular surgery.¹³ In general, it is recommended to treat dry eye before and after cataract surgery to continuously improve ocular surface quality.¹⁴ Treatment includes lid hygiene, topical preservative-free lubricants, ointments, punctal plugs, topical or oral antibiotics, autologous serum, amniotic membranes, and temporary or tarsorrhaphy. Caution should be exercised when using bandage contact lenses due to the susceptibility to infection and topical nonsteroidal anti-inflammatory drug (NSAID) drops due to the possibility of corneal stromal melting.⁷ New treatments have been introduced to help corneal epithelial regeneration including topical insulin eyedrops, thymosin β4, cenegermin-bkbj (a U.S. Food and Drug Administration–approved recombinant human nerve growth factor), aldose reductase inhibitor CT-112, and other growth factors.^15–18

Cornea

Diabetic keratopathy involves 3 main types of corneal tissue dysfunction (1) impaired corneal wound healing, (2) abnormalities of subbasal nerves, and/or (3) corneal endothelial pump dysfunction.^4–6 In diabetic corneas, basement membrane (BM) thickening, multilamination, and reduced anchoring fibrils lead to changes in epithelial adhesion and abnormal wound healing.^5,11 Morishige et al. used the Z-scan to provide a light-scattering index (LSI) for corneal epithelial BM, a quantitative parameter which increases with the severity of DM.¹⁹ It is important to protect corneal epithelium during and after cataract surgery and avoid or treat any corneal epithelial damage promptly.

DM alters the corneal endothelium in both cell density and morphology (eg, polymegethism and pleomorphism).⁵ Diabetic patients are more susceptible to endothelial damage during cataract surgery, and considering this vulnerability, the cataract surgeon should keep the anterior chamber (AC) manipulation and the ultrasonic power to a minimum.²⁰

Lens

A 2- to 5-fold higher incidence of cataracts has been reported in diabetic patients.^3,21,22 The most common type is the senile cataract.²³ Other types of cataract associated with diabetes include the snowflake cataract which is generally uncommon but mostly seen in type 1 DM, posterior subcapsular cataract, and nuclear and cortical cataract.^21,22 Bayraktar Bilen et al. reported a cataractous effect of DM in anterior, nuclear, and posterior regions of the lens by a lens densitometer.²⁴

Accumulation of sorbitol in the diabetic lens creates a hyperosmotic state which causes retention of fluid in the lens fibers and extensive swelling of cortical lens fibers especially in young patients with type 1 DM.²¹ In addition to osmotic stress, oxidative stress, apoptosis of the lens epithelial cells, and production of polyols from glucose play important roles in diabetic cataract formation.^21,22 Papadimitriou et al. proposed a hypothesis that there could be an autoimmune process behind acute bilateral type 1 diabetic cataracts.²⁵

Several studies suggested a correlation between a greater risk of cataract surgery in diabetics and increased fasting blood glucose, increased HbA1c, the prolonged duration of diabetes, and dietary glycemic load.^26–30 On the other hand, there are some studies which showed no significant risk reduction was in incidence of cataract surgery with intensive glycemic control.³¹ Kato et al. suggested that rapid glycemic control can induce an irreversible increase in lens opacification, which is not seen in the slow glycemic control group.³² It is safe to conclude that long-term glycemic control may decrease the incidence of cataract among diabetic patients.

Diabetic patients may experience transient myopic shift due to hyperglycemia, although some studies reported hyperopic refractive changes, mainly on initiation of diabetic treatment.^21,33 Regardless of the type of refractive change, morphologic and functional alterations in the crystalline lens remain the most probable cause.²¹ It is known that lens capsule or BM of the lens is thicker but more friable and prone to inadvertent tear or rupture during cataract surgery in diabetics.^3,21,34

Iris

Iris neovascularization is the major consequence of diabetes on the iris.³³ Diabetes involves not only iris muscle cells but the iris nerves, causing miotic pupils less reactive to mydriatics.³⁵ Su et al., using anterior segment optical coherence tomography (OCT), showed that iris volume was significantly lower in glaucomatous eyes of the diabetic patients when compared with those of nondiabetics, and there was a significant correlation with HbA1c levels.³⁵ Other iris complications associated with DM include pigment deposits on the corneal endothelium and trabecular meshwork due to the release of pigment from the iris and abnormal iris transillumination.^3,33 Owing to the fact that the diabetic pupil is difficult to dilate and may become miotic during phacoemulsification, necessary measures should be taken in advance, which we will discuss further in the perioperative consideration.

Trabecular Meshwork, Angle, and Intraocular Pressure

DM gives rise to microvascular damage of the retina and optic nerve in addition to changes in the metabolism of the retinal ganglion cells and, possibly, increasing the susceptibility to primary open angle glaucoma.^36,37 Hyperglycemia can cause overexpression of extracellular matrix such as fibronectin, by trabecular meshwork cells and cellular proliferation, leading to blockage of aqueous outflow.³⁸ Uncontrolled diabetes with greater HbA1c levels can cause significantly higher intraocular pressures (IOPs).³⁸ On the other hand, posterior segment ischemia in proliferative DR (PDR) leads to neovascularization of iris and development of peripheral anterior synechiae and obstruction of aqueous humor outflow, with consequent secondary angle closure glaucoma.³⁹

Management of concurrent cataract and neovascular glaucoma (NVG) can be challenging and needs a multidisciplinary approach which addresses all concurrent pathologies and ideally includes the following interventions: anti-vascular endothelial growth factor (VEGF) agents to produce temporary regression of neovascularization, phacoemulsification, panretinal photocoagulation (PRP) during pars plana vitrectomy (PPV) or after cataract extraction to further control retinal ischemia and neovascularization, and antiglaucoma surgery.^40,41 Failure to treat the proliferative retinopathy preoperatively increases the risk of its progression after surgery.⁴²

PART II: TIMING OF CATARACT SURGERY AND EFFECT ON QUALITY OF LIFE

Today, attention is being paid to the comprehensive concept of vision-specific quality of life (QoL), which includes various aspects of performance, including physical performance such as reading, driving, and working, along with emotional and psychological well-being, concerns, and social interaction. Although in past decades, timing of cataract surgery in patients with diabetes was more conservative owing to the fear of postoperative complications such as macular edema, there is an increasing tendency toward earlier cataract surgery to improve their QoL and even glycemic control.^43,44

With the advancement of phacoemulsification, the risk of complications in diabetic patients has decreased and the visual and refractive results have improved. On the other hand, cataract formation can obscure the view of the posterior segment causing the retinal evaluation to become more challenging.⁴⁵ Diabetic patients without DR and those with mild nonproliferative DR (NPDR) exhibit similar improvements in their QoL and vision as individuals without diabetes.^42,46 Longitudinal visual function 5 years after cataract surgery was not significantly worse compared with nondiabetics.⁴⁷ The limited number of studies focusing their attention on the effect of cataract surgery on QoL of diabetics has suggested that patients with no DR and mild NPDR show more significant improvements in QoL and a more rapid functional rehabilitation compared with patients with more advanced DR.^48,49

Patients with more advanced DR should be approached with more caution and preferably in collaboration with a retinal specialist.

PART III: PREOPERATIVE CONSIDERATIONS

Diabetic patients should receive careful preoperative evaluation with special attention to the presence of any diabetic ocular pathology, and it is recommended that an experienced surgeon performs the surgery considering the range of anterior segment changes that can be seen in these patients. Before surgery, patients should have good glycemic control and no sign of ocular or periocular infection.

A comprehensive ophthalmologic examination including assessment of visual function, corrected distance visual acuity (CDVA), relative afferent pupillary defect, slitlamp biomicroscopy, gonioscopy (with emphasis placed on the presence of new vessels), tonometry, and detailed dilated fundus examination is crucial. In select cases, ancillary diagnostic evaluations such as fluorescein angiography, OCT, and B-scan ultrasonography may be beneficial. Partnering with a vitreoretinal subspecialist is often the best approach to the complex diabetic patients.²²

A stable tear film is crucial for accurate and reproducible corneal power measurements. Inaccurate keratometry can affect the final intraocular lens (IOL) calculation.^14,50 During periods of unstable glycemic state, transient refractive changes are possible and more importantly alterations in corneal topographic parameters can be a potential source of error in keratorefractive and biometric calculations during these periods. Diabetes can cause transient changes in refractive errors, with hyperglycemia leading to myopia and hypoglycemia leading to hyperopia. It has been reported that diabetic individuals experience both hyperopic and myopic shifts because of hyperglycemia treatment.⁵¹

Sonmez et al. studied diabetic patients to assess the impact of hyperglycemia control on several ocular parameters. Because of hyperglycemia correction, they observed statistically significant changes in topography flat axis keratometry and refraction. Nevertheless, no significant changes were found in lens thickness, pachymetry, vertical and horizontal axis keratometry, IOL power, or AC depth.⁵¹ Although previous research on the influence of blood glucose levels on IOL power is lacking, this study, with its limited sample size, found that hyperglycemia did not exhibit a statistically significant association with changes in IOL power, as indicated by a mean change of 0.50 diopters. This nonsignificant result could potentially be attributed to the small sample size and a lack of statistical power to detect differences in parameters affected by blood glucose status. Nevertheless, it is crucial to take this finding into consideration in clinical practice to enhance patient outcomes. In diabetic patients being treated intensively for hyperglycemia, cataract extractions, as well as other refractive procedures including spectacles prescriptions, should be postponed until blood glucose have normalized and refractive errors have stabilized.^33,51 Sources of error in axial length (AL) measurement and subsequent IOL power calculation error in diabetic eyes include increase in cataract density, eyes filled with silicone oil, and changes of retinal thickness of the macula (diabetic macular edema [DME], epiretinal membrane, macular traction) leading to AL changes.^52–54 However, Attas-Fox et al. reported that AL measurement with optical biometry is less affected by retinal thickening than A-scan ultrasound.⁵⁵

Many studies recommended preoperative PRP in patients with preexisting PDR to avoid rapid progression after cataract surgery.^3,22 If preoperative PRP is precluded by the lens opacity, alternative approaches to PDR include immediate indirect PRP after the surgery, PRP planned and performed within a week after cataract surgery, preoperative panretinal cryopexy, combined cataract surgery with vitrectomy, and endolaser photocoagulation especially for cases with vitreous hemorrhage or posterior pole tractional retinal detachment.^22,56 Macular edema and neovascularization of the iris (NVI) should be adequately treated before surgery. Preexisting DME may be aggravated postoperatively and is associated with a poor visual outcome.⁵⁶ Many studies proved the possibility of macular abnormalities identified on OCT despite unremarkable findings on biomicroscopic funduscopy.^57–59 The routine use of macular OCT in diabetic patients especially those with DR, before cataract surgery, improves diagnosis of preoperative macular pathologies. If possible, they should be treated preoperatively or at least used to counsel patients of the potential limitations of surgery.^60,61

Active NVI increases the risk of intraoperative and postoperative complications. In NVG, medical therapy alone often is ineffective. Topical β-adrenergic antagonists, α2-adrenergic agonists, carbonic anhydrase inhibitors, cycloplegics, and corticosteroids may be used to reduce IOP and inflammation. Historically, NVG treatment was treating proliferative retinopathy through PRP. Anti-VEGF agents, such as intravitreal ranibizumab or bevacizumab or aflibercept, showed promising temporary responses in IOP reduction and regression of neovascularization, generally between 4 to 6 weeks.^39,62,63 However, currently available evidence is uncertain about the long-term effectiveness of anti-VEGF medications, in NVG.⁶⁴ Once NVI regresses, cataract surgery should be considered as early as possible to enable treatment of the proliferative retinopathy. Combining cataract surgery with endoscopic diode laser cyclophotocoagulation is an alternative option when AC angles are closed with mature (fibrosed) vessels.⁶⁵ In select cases of NVG, a combination of glaucoma surgery with phacoemulsification may also be considered after regression of NVI.²¹ However, despite all these considerations, the visual outcomes after phacoemulsification in eyes with NVG are usually questionable.

PART IV: CATARACT SURGERY

As compared with extracapsular cataract surgery, the modern phacoemulsification technique provides better visual outcomes and induces less inflammation and posterior capsule opacification.⁶⁶

Subclinical ocular surface abnormalities in diabetics including decreased epithelial barrier function, BM thickening, and decreased corneal sensation often have a close temporal relation to the development of symptomatic diabetic keratopathy after surgery, including superficial punctate keratopathy, persistent corneal epithelial erosion, and infection. Iatrogenic or de novo epithelial erosions in diabetic patients may be resistant to routine clinical management predisposing these corneas to bacterial and fungal infection.⁶⁷ To avoid this complication, serum glucose control before surgery and paying special care to protect the corneal epithelium during surgery are essential.^67,68 A small pupil is frequent in diabetics making cataract surgery technically challenging.⁶⁹ Pupil enlargement should be considered during cataract surgery using intracameral mydriatics, pupil-stretching techniques, sphincterotomies, or mechanical iris retractors.

Mydriasert (Spectrum Théa Pharmaceuticals Ltd.) containing 0.28 mg tropicamide and 5.4 mg phenylephrine hydrochloride can be inserted in the inferior fornix 1 hour before surgery to avoid repeated instillation of topical eyedrops.

Various studies have proven advantages of intracameral mydriatic solutions over topical regimen including a prompt onset of pupil dilation, stable pupil diameter which is shown to be statistically larger at the end of surgery compared with a topical regimen, decreasing the preoperative waiting period, mitigating ocular surface toxicity, and lower systemic absorption due to reduced quantity of administrations.^70–72 Epi-Shugarcaine solution (Epi-Lido, subsidiary of Harrow, Inc., epinephrine 0.025% and lidocaine 0.75% in fortified balanced salt solution), Lundberg and Behndig's intracameral dilation solution (cyclopentolate 0.1%, phenylephrine 1.5%, and lidocaine 1%), and Mydrane (Laboratoires Théa, tropicamide 0.02%, phenylephrine 0.31%, and lidocaine 1%) are preservative-free ophthalmic combinations for intracameral administration.⁷³ Preservative-free lidocaine alone is proven to provide sufficient mydriasis for phacoemulsification in some patients with type 2 diabetes.⁷¹ Topical and intracameral NSAIDs such as Omidria (phenylephrine 1.0% and ketorolac 0.3%) can inhibit prostaglandin release and subsequent miosis during cataract surgery.^74–76 Intracameral epinephrine alone as a mydriatic agent may increase the risk of macular edema in diabetic patients.⁷⁷ Further mydriasis can be achieved with cohesive, high molecular weight ophthalmic viscosurgical devices.⁷⁸ Pupil stretching techniques or dilating devices (eg, iris retracting hooks and pupil expansion rings) should be considered if the above interventions fail.⁷⁹

DM is a systemic risk factor for anterior capsular phimosis, especially in the presence of DR; to prevent IOL displacement and posterior capsular opacification (PCO), capsulorhexis size should be targeted between 5 and 6 millimeters to prevent capsular phimosis and to provide a good view of the retinal periphery, but to be smaller than the IOL optic diameter.⁸⁰ A larger than average capsulorhexis and a large diameter optic may be helpful for diagnosis and treatment of peripheral retinal pathology postoperatively.^80,81

In case of a white cataract or a dense posterior subcapsular cataract, vital staining of the anterior capsule should be considered.⁸² Cortico-capsular and cortico-nuclear adhesions can be sticky in diabetic cataracts causing hydrodisection and hydrodelineation procedures to be more challenging.⁸³

The higher the nuclear grades of cataracts (3 and more), the more the risk of endothelial cell damage and posterior capsular complications. Using newly designed phacoemulsification machines, especially with active–fluidics systems, increases the efficacy and safety of phacoemulsification in these cases.^84,85 To decrease the ultrasound power, phacoemulsification time, and stress on the zonular fibers and endothelial cell damage, phacoemulsification-chop techniques with endocapsular phacoemulsification are superior for the hard, leathery brown nuclear cataract.^86–88

Factors affecting the amount of postoperative inflammation leading to incidence or progression of retinopathy are duration of surgery, wound size, and posterior capsular rupture or vitreous loss.⁸⁹ The surgeon's expertise has influence on surgical time, the chance of intraoperative complications, endothelial stress, and epithelial trauma. It is of the utmost importance to minimize surgical trauma in diabetic eyes.

IOL Choice

Current materials used for foldable IOL optics are of 3 types including silicone, hydrophobic acrylic, and hydrophilic acrylic. The biocompatibility of these materials in diabetic patients has been evaluated in several studies.

Hydrophilic acrylic lens opacification seems to be seen more often in diabetic patients.^90–92 It may be related to metabolic disturbances including higher level of phosphorus in the serum and aqueous humor of diabetic patients, particularly those with PDR and disruption of the blood–aqueous barrier leading to intraoptic precipitation of calcium and phosphate.⁹⁰ It has been suggested to be cautious about using hydrophilic acrylic IOLs in diabetic eyes.^92,93

Silicone oil droplets can remain stuck to the posterior surface of a silicone IOLs during PPV. Since diabetic patients are more prone to needing vitreoretinal surgery using silicone oil, these types of IOLs may be relatively contraindicated in such individuals.⁹⁴ Hydrophobic IOLs are associated with minimal visually significant PCO.⁹⁵ In addition, hydrophobic acrylic lenses have a low propensity for silicone oil adhesion and considering all the above, they may be the IOL of choice for diabetic patients. A larger diameter of the IOL optic provides a larger optical area for facilitating visualization and treatment of DR. PCO seems to develop more severe and more often in diabetic patients than nondiabetic patients.^96,97 Square-edged design has a significant preventive effect against PCO, regardless of the composition of the IOL material.^92,98 Larger optic hamper capsular adhesion and bend formation result in less PCO formation.⁹² Lauwers et al. introduced a method called bag-in-the-lens implantation technique, which, although it requires posterior capsulorhexis, had acceptable visual results in diabetic patients, and at the same time, it prevents posterior capsule opacity.⁹⁹ According to Leysen et al., eyes that underwent bag-in-the-lens IOL implantation did not require Nd:YAG laser posterior capsulotomy, unlike those treated with the standard lens-in-the-bag technique.¹⁰⁰

Toric IOLs may correct for preexisting regular corneal astigmatism at the time of cataract surgery providing a better postoperative uncorrected distance visual acuity and reducing the need for distance spectacles.¹⁰¹ The prevalence of postoperative complications was not significantly different between toric IOL implantation and nontoric IOL implantation groups in a meta-analysis of 6 studies.¹⁰¹ However, secondary surgical intervention is more prevalent in the toric group for realignment. In patients with DR who may undergo vitreoretinal surgery in the future, significant changes of corneal contour are a cause for concern when using 20-gauge vitrectomy. 23-gauge, 25-gauge, and 27-gauge microincisional vitrectomy surgery showed less surgically induced astigmatism and topographic changes.^54,102,103 Unlike multifocal IOLs, toric IOLs are not associated with reduced contrast sensitivity, and they improve quality of vision.^101,104 Hence, toric IOLs can be used even in patients with retinal comorbidities but with good visual potential.

Recently multifocal IOLs (mIOLs) are commonly used to achieve precise and desired refractive and visual outcomes, but they are advised against in patients with retinal disorders because it is believed that they reduce contrast sensitivity.¹⁰⁵ Severe DR is a relative contraindication for mIOL implantation.¹⁰⁶ It is still controversial whether we should advise against mIOLs in a diabetic patient who is at high risk of developing macular edema or in patients with present macular edema. Optic design of mIOLs is likely to make fundus visualization difficult during postoperative laser treatment or vitrectomy.¹⁰⁷ Given that new advanced extended depth-of-focus lenses compromise the postoperative contrast sensitivity less, many surgeons may now consider implanting these IOLs in patients with mild ocular comorbidities such as mild NPDR.^108,109 Further research is needed to address the aforementioned concerns regarding the use of mIOLs in diabetic eyes.

IOL Implantation Site

For patients with DM, the ideal site is in-the-bag fixation of the optic and the haptic which reduces the incidence of central PCO.¹¹⁰ Single-piece IOLs are not designed for sulcus implantation, and this implantation location should be avoided especially in diabetics.¹¹¹

In general, IOL implantation behind the iris plane seems to better about the anatomy of the eye. However, the scleral-sutured posterior chamber lens implantation has some risk of complications, such as vitreous bleeding, choroidal hemorrhage, retinal detachment, and chronic macular edema caused by vitreous traction.^112,113 To avoid suture-related complications, recently, there has been a trend toward the use of suture-less methods of scleral fixation such as the glued IOL and Yamane techniques.^114,115 Iglicki et al. demonstrated that a suture-less IOL-flanged technique with a 30-gauge ultrathin walled needle has significantly less complications in diabetic patients, compared with a 27-gauge needle technique.¹¹⁶

During the past few 2 decades, studies mostly have focused on 2 secondary IOL implantation techniques: angle-supported AC IOLs and scleral-fixated IOLs (SF IOLs). Given the current information, in the absence of capsular support, choosing between AC IOLs, iris-sutured posterior chamber IOLs, and SF IOLs depends on the experience and comfort of the surgeon. Suture fixation of the lens to iris and sclera should be avoided in patients with PDR.¹¹⁷ Flexible, open-loop AC IOLs showed excellent outcomes in nondiabetic patients when correct surgical techniques were used.^118,119 However, they are near the angle and may increase the risk for bullous keratopathy, glaucoma, and peripheral anterior synechiae.¹²⁰ The use of AC IOLs in diabetic patients is controversial.¹²¹ Some studies considered diabetes as a contraindication for iris-claw lens implantation.¹¹² It is recommended that iris claw lenses and iris fixation be avoided in patients with DM due to the increased risk of iris neovascularization, cystoid macular edema (CME), and poor mydriasis; however, midperipheral iris fixation may reduce the concern for angle-related complications in comparison with AC IOLs.^122,123

Unfortunately, most of these concerns are theoretical, and information regarding the use of iris claw lenses in diabetics is inadequate.

Femtosecond Laser-Assisted Cataract Surgery in Diabetic Patients

Phacoemulsification can increase in inflammatory factors in the AC and vitreous body. This procedure generates heat, radiation, and shock waves affecting the vitreous and retina.^124,125 Femtosecond laser-assisted cataract surgery (FLACS) has some proven advantages, which are as follows: (1) self-sealing, stable corneal incisions with reduced induced astigmatism, and a multiplanar configuration.¹²⁶ (2) A more precise, reproducible, well-centered anterior capsulotomy with overlap of the anterior capsule with the IOL optic is compared with conventional manual continuous curvilinear capsulorhexis.¹²⁶ (3) Softening and liquefaction of the cataractous lens leading to optimize phacoemulsification parameters reduce the cumulative release of ultrasound energy and complications.^126–129

However, femtosecond laser pulse shockwave can damage anterior segment structures such as the iris and ciliary body, and microbubbles generated by femtosecond laser can mediate the inflammatory cascade leading to a more significant prostaglandin release compared with conventional phacoemulsification.¹³⁰ FLACS requires suction of the cornea, and the subsequent increase in IOP can affect the blood supply of the retina and optic nerve. Some studies reported FLACS to be safe and effective in diabetic patients with no DR or mild DR with earlier visual recovery and faster recovery of the retinal and choroidal thickness.¹³¹ FLACS may also induce or worsen the postoperative dry eye, and in diabetic patients with ocular surface problems, it should be taken into account.¹³²

Combined Phacoemulsification and Intravitreal Injection

Several studies have proven that intravitreal injections of corticosteroids and anti-VEGF are safe and effective for the treatment of DME and DR.^133–135

A systematic review and meta-analysis of studies on intravitreal bevacizumab or ranibizumab treatment at the end of cataract surgery for patients with DR showed that the anti-VEGF group had significantly lower mean macular thickness at various timepoints, lower retinopathy/maculopathy progression, and improved visual acuity compared with cataract surgery alone. No significant changes in IOP or adverse effects were observed, suggesting that this treatment may be a safe and effective strategy for diabetic patients, especially patients with DR undergoing cataract surgery.¹³⁶

A systematic review with meta-analysis reviewed the studies that investigated the results of cataract surgery combined with either an anti-VEGF therapy or a dexamethasone implant in patients with DME. The dexamethasone implant group showed a significant reduction in macular thickness at 3 months, whereas the anti-VEGF group did not show a significant change in macular thickness, although there was no significant difference in visual gain at 3 months.¹³⁷ There has been a significant improvement in central macular thickness (CMT) and visual acuity in patients with DME treated with intravitreal injection of dexamethasone or triamcinolone acetonide combined with phacoemulsification.^138–142 Both intravitreal triamcinolone acetonide and bevacizumab were equally effective in improving visual acuity, but only triamcinolone acetonide showed a persistent reduction in CMT with fewer injections required in the follow-up period.^143,144

Although intravitreal steroids can increase IOP, their longer duration of action and greater effect on macular thickness with fewer injections give them an advantage over anti-VEGF agents. Currently, ranibizumab and dexamethasone implants are the 2 on-label drugs with the most clinical evidence and should be considered first.¹⁴⁵

The prophylactic use of anti-VEGF in diabetic patients undergoing phacoemulsification remains a subject of debate. Although some studies indicate that anti-VEGFs show short-term structural benefits 1 month after cataract surgery, the consistency of this effect on visual acuity is uncertain. Some argue that anti-VEGF effectively prevents postoperative macular edema in diabetic patients after cataract surgery, and for visual acuity outcomes, additional anti-VEGF intervention is linked to improved postoperative CDVA.^146,147

PART V: POSTOPERATIVE

Perioperative prophylaxis for endophthalmitis includes topical, intraocular, subconjunctival, and oral antibiotic agents. The use of intracameral antibiotics during cataract surgery has been associated with a lower incidence of postoperative endophthalmitis.¹⁴⁸ Topical antibiotics are usually used for the first week postoperatively until the surgical wounds are healed, and then, it should be discontinued without tapering to prevent the development of resistant bacteria.¹⁴⁹ Management of postoperative inflammation is crucial to prevent serious adverse events, such as posterior synechia, uveitis, cystoid macular edema, and secondary glaucoma.¹⁵⁰

Kessel et al. conducted a systematic review of literature and found high-quality evidence that topical NSAIDs are more effective in preventing pseudophakic CME than topical steroids and also found low to moderate quality of evidence that topical NSAIDs are more effective in controlling postoperative inflammation after routine cataract surgery.¹⁵⁰

The Royal College of Ophthalmologists recommends the use of topical NSAIDs before and after surgery if patients are at increased risk of CME (eg, diabetics).¹⁵¹ A meta-analysis found that topical steroids in combination with NSAIDs prevented 75.8% of CME events in diabetic patients without preoperative DME.¹⁵² Although it is unknown which topical NSAID is most effective, Bromfenac and Nepafenac possess pharmacokinetic advantages over other NSAIDs. Nepafenac 0.1% is recommended to be taken 3 times daily beginning the day before surgery and continuing for 3 months in combination with topical steroids to prevent macular edema.^145,153,154

Symptoms of foreign body sensation and irritation are often due to postoperative dry eye syndrome, induced or worsened by the act of cutting the corneal nerves during clear corneal cataract surgery.¹⁵⁵ The medication options for postoperative dry-eye syndrome are as follows: topical artificial tears (preferably preservative-free), lubricating gels or ointments, topical anti-inflammatory medications, and systemic treatments.^155–160

Visual Prognosis After Cataract Surgery

In general, the visual prognosis after phacoemulsification in diabetic patients is favorable. However, the presence of significant DR hampers postoperative vision improvement.

Diabetics with no DR had the same odds of postoperative 20/20 vision as patients without diabetes, and in eyes with DR, increasing severity of retinopathy was associated with decreased odds of achieving 20/20 vision postoperatively.^161,162 Liu et al. presented that patients with DR are less likely to achieve a 20/20 CDVA postoperatively compared with those without diabetes. However, diabetic patients gain as many lines of CDVA as nondiabetics from cataract surgery.¹⁶³ In a study of patients with mild to moderate retinopathy, but without previous macular edema, they had the same visual outcome as nondiabetic patients at 6 months.¹⁶⁴

Progression of DR After Cataract Surgery

Determining the progression of DR after intraocular intervention is the primary concern before considering any surgical options.^165–167 The disruption of the inner blood–retinal barrier is caused by the diffusion of inflammatory mediators from the AC to the retina. The heightened inflammation after cataract surgery may lead to several conditions, including cystoid macular edema, exacerbation of DR, and DME.¹⁶⁸ However, the results regarding the occurrence and progression rate of DR after phacoemulsification are inconsistent, and there is an ongoing debate regarding the effect of phacoemulsification on DR progression and occurrence.^169–171 In studies evaluating the progress of DR after phacoemulsification, 12% to 36.4% of patients progressed within 1 year.^171,172

Jeng et al. found that patients without DR undergoing cataract surgery faced a significantly higher risk of developing NPDR if they experienced complications during the procedure, with a hazard ratio of 5.40 for complicated surgery compared with 1.42 in cases without complications.¹⁷³ A meta-analysis conducted by Wang et al., in 2016, revealed that operated eyes showed a higher progression rate of DR after phacoemulsification (odds ratio 1.53, 95% CI 1.04-2.26, P = .03) compared with the nonoperated contralateral control eyes (odds ratio 1.86, 95% CI 1.03-3.37, P = .04).¹⁷⁴

It has been demonstrated that several key factors are associated with the progression of DR after phacoemulsification, including inadequate diabetes control, elevated levels of HbA1c, the initial severity of DR, insulin administration for diabetes management, high levels of low-density lipoprotein cholesterol, DM duration, and surgical complications and proficiency.^{169,172,173,175,176}

Postoperative DME

After cataract surgery, diabetic patients may experience DME and/or pseudophakic CME (PCME), and it can be difficult to differentiate between them.¹⁷⁷ Findings on clinical examination, such as microaneurysms and lipids, are in favor of diabetic edema, while petaloid fluorescein staining around the fovea and optic nerve staining on fluorescein angiography can be suggestive of PCME.¹⁷⁸ In OCT, a greater CMT to retinal volume ratio increased outer nuclear layer thickness compared with the Henle layer, exclusive inner nuclear layer cysts, intact hyperreflective outer retinal bands, and the presence of subretinal fluid suggests PCME, while characteristics such as a higher parafoveal outer nuclear layer–inner nuclear layer thickness ratio, microaneurysms, hard exudates, microfoci, additional ganglion cell or retinal nerve fiber layer cysts, lack of subretinal fluid, mainly outer nuclear layer cysts, and disruption of photoreceptor layers are indicative of DME.^{176,177,179–182} In diabetic patients without retinopathy, the relative risk of PCME is 1.8, while it rises to 6.23 for patients with NPDR, and to 10.34 for patients with PDR.^{154,183–185}

Most patients with concurrent DME at the time of cataract surgery have significantly compromised vision after 1 year, and spontaneous resolution is rare.¹⁷⁷ The DRCR.net study showed 10% to 12% of eyes with noncentral DME before surgery progressed to central-involved ME after surgery. Patients with DR are more likely to develop central-involved macular edema after cataract surgery if noncentral DME is present immediately before cataract extraction or if they have a history of DME treatment.¹⁸⁶ Hence, diagnosis and management of DME before cataract surgery is mandatory; however, the presence of a preexisting DME does not warrant delaying cataract surgery if there is a clinical indication.¹⁷⁷ Khattab et al. suggested that there may be not significant difference in visual outcome or macular thickness between treatment of DME before or after cataract surgery.¹⁸⁷ However, it is important to follow-up diabetic patients after surgery at regular intervals for DR progression and macular edema.

Combined PPV and Cataract Surgery in Diabetic Patients: Challenges and Outcomes

PPV is indicated for some cases of vitreous hemorrhage, tractional retinal detachment, combined retinal detachment, DME, and premacular hemorrhage.¹⁸⁸ The most common complication of this surgery is the progression of cataracts, and cataract surgery in vitrectomized eyes is more challenging due to the deep AC, zonular dehiscence, mobile posterior capsule, and prior posterior capsule trauma from vitrectomy surgery.^189–191 Therefore, in some cases, combining PPV with cataract extraction may be a wise decision.¹⁸⁹ This approach, however, has some limitations, including difficulties with capsulorhexis due to diminished red reflexes, an increase in the risk of wound dehiscence after vitrectomy maneuvers, intraoperative miosis after cataract extraction, potential complications associated with vitreoretinal surgery such as hyphema and corneal edema/Descemet folds impacting corneal transparency, as well as tamponade issues and prismatic effects/light reflexes.¹⁹¹ There has been some evidence of improved visual acuity, a reduced incidence of NVG, and increased procedural convenience in a multicenter study evaluating the combination of PPV and cataract surgery in patients with PDR and mild-moderate cataracts. Hence, this study suggests that the combination of phacoemulsification and cataract surgery is a favorable option for such patients.¹⁹²

Endophthalmitis

Endophthalmitis after cataract surgery is a rare yet formidable complication that poses a significant threat to visual outcomes, with potential consequences such as vision loss or even eye loss. The incidence of postoperative endophthalmitis varies globally, ranging from 0.0016% to 0.28%, and is influenced by factors such as preventive measures, diagnostics, ethnicity, and socioeconomic conditions.^193,194 It was found that diabetes is an independent risk factor for endophthalmitis after cataract surgery, which can result in an increase of threefold in endophthalmitis rates.¹⁹³ Diabetic patients account for 14% to 21% of all patients who develop postoperative endophthalmitis after cataract surgery.^195,196 Hyperglycemia increases the susceptibility to infection.¹⁹⁷ A possible explanation for this association is a reduction in immune responses mediated by T cells and humoral immunity, as well as decreased neutrophil adhesion, chemotaxis, phagocytosis, and intracellular bactericidal activity.^{193,194,198–200} A diabetic patient also has impaired wound healing and a higher rate of conjunctival colonization with Staphylococcus aureus, Enterococci, and certain Streptococci, which increases the risk of infection after ophthalmic surgery.^200–202 Diabetes, per se, is the primary risk factor for developing postcataract surgery endophthalmitis; however, it has been demonstrated that male sex, DR, history of hypertension, rapid reduction in preoperative blood glucose, and insulin treatment are risk factors for developing endophthalmitis among diabetic patients.^{200,202–205} The Endophthalmitis Vitrectomy Study indicates that vitrectomy proves to be more efficacious than tap–biopsy in patients initially presenting with light perception-only vision, irrespective of their diabetic status.²⁰⁶ In the absence of further evidence, diabetic patients with better vision than light perception may benefit from vitrectomy as an initial treatment, but it is also reasonable to treat such patients with tap–biopsy and intravitreal injection of antibiotics as an alternative treatment.²⁰⁷ The risk of rapid retinopathy progression and poor visual outcomes after endophthalmitis are significantly increased by DR, and it has been demonstrated that individuals with diabetes have a 1.55-fold greater chance of experiencing reduced final visual acuity than individuals without diabetes.²⁰⁷ In addition to the standard precautions (sterile technique, preoperative iodine, and intracameral moxifloxacin), it is sensible to address other factors, such as managing blood glucose and hypertension before cataract surgery to reduce the risk of postoperative endophthalmitis. Early identification of infectious endophthalmitis and a quick referral to a retina specialist for appropriate treatment, including antibiotics and potential vitrectomy, are crucial for effective management.²⁰⁶

CONCLUSION

This review underscores the complex interplay between diabetes and cataract formation, emphasizing the need for meticulous preoperative planning, careful surgical technique, and postoperative management in diabetic patients. Despite advancements in surgical techniques, diabetic patients present unique challenges that require tailored management. Optimizing glycemic control and adopting a personalized approach are key to enhancing surgical outcomes and improving the QoL for patients with diabetic cataract. Continued research in this area is vital to further refine these strategies.