Safety and efficacy of keratorefractive surgery in diabetes mellitus: A clinical review

Abstract

Keratorefractive surgery is typically performed to correct refractive errors, resulting in good postoperative outcomes. Certain conditions, such as autoimmune diseases, metabolic diseases like diabetes mellitus (DM), and the use of some drugs, may be absolutely or relatively contraindicated for refractive surgery. DM is a multisystemic disorder affecting various organs and can result in retinopathy, nephropathy, and neuropathy. Persistent hyperglycemia leads to various pathophysiological changes that can alter the biomechanical profile and the wound healing process of the cornea. Proper patient counselling, optimizing blood glucose levels, and frequent follow-up visits to monitor and manage potential complications, such as dry eye, non-healing epithelial defects, and neurotrophic keratitis, are essential for refractive surgeons. Laser-assisted in situ keratomileusis is preferred over photorefractive keratectomy due to its faster healing process. Cataract surgery in people with diabetes warrants various preoperative, intraoperative, and postoperative considerations for the best visual outcomes. This review focuses on the current evidence pertaining to various structural and functional corneal changes occurring in diabetics and their impact on keratorefractive procedures, thus providing a unified, clinically oriented framework to guide refractive surgeons in risk stratification, procedure selection, and postoperative management in patients with DM.

Key Words: Diabetes mellitus; Refractive surgery; Diabetic keratopathy; Photorefractive keratectomy; Advanced glycation end products

Core Tip: Although routinely performed, keratorefractive surgeries pose challenges, especially in diabetics. Diabetes mellitus can result in keratopathy and affect the corneal healing process, which puts refractive surgeons in a dilemma over whether to go ahead with the surgery or not. Although a relative contraindication, refractive surgeries can be performed on diabetics with proper glycemic control and strict postoperative monitoring. Various drugs and molecules are efficacious in cases of diabetic keratopathy.

INTRODUCTION

Diabetes mellitus (DM) is one of the most prevalent metabolic diseases worldwide, which can have deleterious effects on various bodily systems if not controlled. Lifestyle and dietary changes are to blame for this public health pandemic, with India emerging as the diabetic capital of the world[1,2]. Keratorefractive surgery involves altering the epithelial and stromal layers of the cornea to correct refractive errors, which typically yields good postoperative outcomes. DM can influence corneal physiology and wound healing, making refractive surgery outcomes less predictable. This can lead to various complications, including dry eye disease, persistent epithelial defects, and neurotrophic keratopathy after refractive surgery. Refractive surgeries can be performed on diabetics after strict glycemic control, and surgeons need to approach carefully to manage any complications that may arise.

METHODOLOGY

An extensive review of literature was carried out using several electronic databases such as PubMed, EMBASE, ScienceDirect, Google Scholar, Web of Science, Cochrane, and Reference Citation Analysis. The search period was set from 1979 to 2025. Researchers utilized medical subject headings in their PubMed studies. The terminologies used for the search were ‘diabetes mellitus’, ‘refractive surgery’, ‘diabetic keratopathy’, ‘diabetic cataract’, and ‘diabetic retinopathy’. Many pertinent clinical studies were assessed, with their abstracts examined for relevance before being incorporated into this review. Out of 1542 articles reviewed, 75 were found to be relevant and included in the study. Studies were considered if they looked at keratorefractive or cataract surgery results in patients with diabetes, or discussed diabetic corneal changes related to refractive surgery, such as safety, effectiveness, vision results, and possible complications. Only human clinical studies written in English and published from 1979 to 2025 were included. Animal studies, laboratory experiments, single case reports, publications in languages other than English, abstracts, opinion pieces, and studies that did not present outcomes specific to diabetes were all excluded. Titles and abstracts were first checked to determine their relevance, after which the full texts were reviewed according to specific eligibility criteria. When multiple sources had similar information, preference was given to the latest or most thorough studies.

DISCUSSION

DM is among the most common metabolic diseases prevalent today in the world, which, if not treated, can lead to devastating complications affecting various organ systems. Lifestyle changes over the years, with increased calorie intake, lack of exercise, and sedentary habits, have led to a sharp spike in cases of diabetes worldwide[3]. DM occurs due to the failure of the pancreas to synthesize insulin [type 1 DM (T1DM)] or due to resistance to insulin despite normal blood levels [type 2 DM (T2DM)][4]. An acute rise in blood glucose levels (hyperglycemia) can result in ketoacidosis, whereas hypoglycemia can result in coma, which are life-threatening conditions. Chronic uncontrolled DM can affect and damage various organ systems, leading to neuropathy, nephropathy, retinopathy, and keratopathy[5].

Diabetic retinopathy (DR) is a common ophthalmological complication in DM and is the leading cause of blindness in developed countries. The effects of DM on the anterior segment, including the conjunctiva, cornea, and tear film, are not well recognized but can have a significant impact on overall ocular surface health and implications for ocular surgeries[6,7]. Peripheral neuropathy is the most common type of neuropathic presentation associated with DM, with half of the diabetic population presenting with it after a 25-year follow-up[8]. Chronic hyperglycemia is the primary underlying cause of this pathology, with the activation of complementary pathways that further induce and exacerbate this damage.

OCULAR PATHOPHYSIOLOGICAL CHANGES IN DM

Changes caused by diabetes in the tear film and corneal layers can have a direct impact on the safety and predictability of refractive surgery. Dry eye syndrome often affects people with diabetes and is caused by multiple factors. Alterations in the lipid layer and reduced goblet cell densities result in an unstable tear film. Reduced trophic effects due to trigeminal neuropathy impair the functioning of the lacrimal functional unit, resulting in decreased basal secretion and dry eyes. Chronic hyperglycemia also results in increased pro-inflammatory cytokines in the tear film along with increased tear film hyperosmolarity[9]. The corneal epithelium is a crucial structure responsible for maintaining corneal clarity and homeostasis; and in the event of any corneal injury, rapid healing is essential. However, in the case of diabetic corneas, there is delayed healing of corneal epithelial defects, which are resistant to conventional treatment options, leading to persistent corneal epithelial defects that can result in infections, thinning, and perforation[10-12]. This altered healing process occurs due to a combination of various cytokines and growth factors such as platelet-derived growth factor, interleukin-6 and interleukin-10, thymosin-β4, epidermal growth factor, transforming growth factor-beta etc., causing modulation of the downstream signaling process and accumulation of advanced glycation end-products (AGEs), ultimately affecting the cell migration, proliferation, and differentiation, thus delaying corneal healing[13,14]. The subepithelial corneal nerve plexus is responsible for corneal sensations, along with the release of specific growth factors and neurotrophins that are responsible for maintaining corneal integrity. In cases of DM, there is a reduction in sub-basal nerve fibre density, along with a decrease in length and branch density, which can ultimately lead to reduced corneal sensation and recurrent, non-healing epithelial defects[15,16]. Corneal confocal microscopy is a non-invasive, dependable, and sensitive tool for assessing nerve fibre density changes in cases of DM, thus serving as a reliable surrogate for evaluating diabetic neuropathy[17,18]. Diabetic patients show notable alterations in the stroma. Increased central corneal thickness (CCT) occurs in DM due to epithelial and endothelial dysfunction, leading to stromal oedema[19]. Additionally, the increased production of AGE and corneal crosslinking induced by glycation contributes to an increased CCT[20]. Long duration of diabetes (> 10 years) and T2DM have been associated with increased CCT and endothelial dysfunction, respectively[21]. The stromal nerves appear twisted and enlarged, and individuals with diabetes show higher levels of matrix metalloproteinase-3 and matrix metalloproteinase-10[22]. Changed and variable biomechanical characteristics of the cornea can be seen in DM as well. These are examined using the ocular response analyser, which measures both the corneal resistance factor and corneal hysteresis[23]. Diabetics also show alterations in the endothelial lining of the cornea. Pleomorphism and polymegathism are responsible for compromised endothelial function, leading to corneal oedema and increased CCT. A reduction in endothelial cell density is also seen in DM, which can result in corneal decompensation after corneal or cataract surgeries[24,25]. Collectively, these changes create a fragile ocular surface that predisposes diabetic patients to postoperative epithelial breakdown, prolonged inflammation, and infection, thereby necessitating stricter preoperative screening and prolonged postoperative lubrication and surveillance compared to non-diabetic patients.

OCULAR SURGERY IN DM

The alterations in the corneal tissue occurring in diabetics pose a challenge in such patients who undergo keratorefractive surgeries. Diabetic patients undergoing such procedures are at increased risk of delayed wound healing and post-surgical infections due to altered immune response in such patients. The indications, choice of procedure, and necessary precautions to be taken during such procedures need to be addressed[26,27].

KERATOREFRACTIVE SURGERY IN DM

The recommendations regarding refractive surgeries, such as photorefractive keratectomy (PRK) and laser-assisted in situ keratomileusis (LASIK) in diabetic patients, as given by the Food and Drug Administration (FDA) and American Academy of Ophthalmology, were not that clear. They relied on limited case reports and lacked clarity. Refractive surgery in diabetics remains controversial due to its tendency to affect ocular issues and physiological processes that are critical for surgical safety, refractive predictability, and postoperative healing. Additionally, chronic hyperglycaemia impairs corneal wound healing, immune defence, and corneal innervation, increasing the risk of delayed epithelial healing, infection, and neurotrophic complications. Diabetes also alters corneal biomechanics through collagen glycation and causes refractive instability due to fluctuating glucose levels, reducing surgical predictability. In addition, coexisting DR or macular edema may limit visual outcomes. As a result, diabetes is regarded as a relative contraindication, so patients must be carefully chosen and thoroughly counselled. Recently, an extensive literature review has provided detailed insights into the results and visual outcomes in such patients, facilitating a better understanding[28]. In the initial period, the FDA identified a specific group of ocular and systemic diseases as absolute and relative contraindications for refractive surgeries based on recommendations from the first excimer laser companies. The systemic diseases include autoimmune and connective tissue disorders, such as systemic lupus erythematosus, rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, Sjögrens syndrome, and systemic vasculitis. DM, immunosuppression, atopy, allergic conjunctivitis, and use of specific medications are considered relative contraindications or risk factors[28].

The PRK procedure involves the removal of the epithelium, which is a primary concern in diabetics, as it may result in poor healing in the postoperative period, potentially leading to a dense stromal haze (Figure 1). On the other hand, the LASIK procedure involves the creation of a thin corneal flap, which results in a faster postoperative recovery; however, it can also lead to issues in the postoperative period for individuals with diabetes. Surgeons may perform excimer laser procedures on patients with diabetes, but they need to exercise care due to potential complications that can occur during or after the operation[28]. Although LASIK offers faster epithelial recovery than PRK, it also introduces flap-related risks such as epithelial ingrowth and neurotrophic epitheliopathy, which may be amplified in diabetes. Conversely, PRK avoids flap complications but exposes the stroma for a prolonged period, increasing haze and infection risk. Therefore, neither procedure is universally superior in diabetes, and individualized risk profiling is essential.

Figure 1 The photorefractive keratectomy procedure involves the removal of the epithelium, which is a primary concern in diabetics, as it may result in poor healing in the postoperative period, potentially leading to a dense stromal haze. A: Surgeon putting alcohol in well for epithelial removal during photorefractive keratectomy; B: Laser ablation to the stromal bed post-epithelial removal during photorefractive keratectomy.

CHALLENGES DURING KERATOREFRACTIVE SURGERY IN DIABETICS

Individuals with uncontrolled diabetes may experience refractive changes, unpredictable results from ablation procedures, slower healing times, nerve-related changes, and worsening retinopathy.

Altered visual outcomes due to varying blood glucose levels

Short-term visual changes can occur with significant fluctuations in blood glucose levels. Transient hyperopia may occur in patients once their blood sugar levels are uncontrolled, particularly in cases of severe hyperglycemia, which results from lens hydration and a decrease in refractive power[29]. The extent of hyperopic change depends upon the pre-treatment glycated haemoglobin (HbA1c) levels and the reduction rate of blood glucose levels over the first 7 days of treatment. Temporary hyperopia can be treated with glasses or contact lenses, but permanent changes after refractive surgery cannot be corrected this way. Hence, maintaining controlled blood glucose levels is necessary both before and after refractive surgeries[30].

Low predictability of corneal ablation

The dysfunctional endothelium causes stromal hydration and increased CCT, along with molecular and structural changes in the corneal tissue of diabetics, which results in an altered response to laser energy used during refractive surgery (Figure 2)[31,32]. Although LASIK has a favourable response among diabetics, 10%-28% of cases require enhancement surgeries due to the reasons mentioned above[33,34].

Figure 2 Cap cut in progress after completing the lenticule cut and the lenticule side cut in refractive surgery (small incision lenticule extraction).

Delayed corneal healing in the post-surgical period

The delayed wound healing effect due to DM can result in a myriad of complications, such as punctate erosions, delayed epithelial healing, persistent epithelial defects, and neurotrophic keratopathy after PRK/LASIK[28]. Epithelial complications may arise during the intraoperative period due to pre-existing or subclinical epithelial basement membrane dystrophy or due to the shearing effect of the microkeratome[35,36]. In the postoperative period, these complications may arise due to the resection of the nerves, resulting in dry eye or neurotrophic keratopathy[37,38]. Different studies report varying results of LASIK and related complications, which may vary depending on the age of the patient and the type of microkeratome being used (nidek vs hansatome)[39]. Although LASIK, compared to PRK, has the disadvantage of creating a corneal flap and stromal ablation, which decreases the overall biomechanical corneal strength, this can result in keratectasia[40]. However, the only advantage of DM is that the AGEs-related stromal fibre crosslinking strengthens the corneal biomechanics, thus having a protective effect against keratectasia in LASIK[41].

Increased rate of epithelial ingrowth among diabetics

Epithelial ingrowth is more commonly observed in diabetic patients after refractive surgery compared with non-diabetic patients (0.5%), likely due to delayed wound healing in the former[42]. Epithelial ingrowth tends to occur more frequently in people with T1DM, so lamellar surgeries should either be avoided or performed with great care in diabetic patients. However, in the long term, visual outcomes and complication rates do not vary significantly between T1DM and T2DM[43].

Altered corneal innervation

Diabetic keratopathy represents a form of neuropathy that can result in reduced corneal sensitivity depending upon the duration of DM and the stage of DR[44-46]. As already discussed, the aldose-reductase pathway, polyol accumulation in the corneal tissue, and the accumulation of AGEs cause epithelial edema and damage to the basement membrane, resulting in poor epithelial healing and persistent defects[47]. The resection of corneal nerves during LASIK results in iatrogenic dry eye, also known as LASIK-induced neurotrophic epitheliopathy, which exacerbates pre-existing dry eye disease[38].

Progression of DR

Worsening of DR might occur following LASIK procedures. This is attributed to the increased suction during the LASIK procedure or while using a femtosecond laser. The suction ring used may result in raised intraocular pressure to critical values, leading to ischemia and progression of DR. Surgeons should carefully examine any pre-existing DR changes and their progression before and after the surgery[48].

APPROACH TO KERATOREFRACTIVE SURGERY IN DM

Surgeons should approach great caution when dealing with refractive surgery in diabetics, as the complication rate is higher in such patients when compared to normal patients (47% vs 6.9%)[49]. Strict screening should be performed on individuals with diabetes, including a detailed vision assessment, slit-lamp examination, tear film assessment, epithelial tests, and retinal examination, which can help identify the right candidates for surgery and minimize complications. Providing counselling is crucial because patients should be made aware of potential risks and complications that could occur after surgery. Clinicians should adopt a conservative approach in patients who may be at risk of potential complications after surgery. Most authors recommend that keratorefractive surgery be performed only in patients with well-controlled DM, typically defined as an HbA1c level of ≤ 7.0%. Patients with HbA1c levels between 7.1% and 8.0% may be considered on a case-by-case basis with careful risk stratification, while levels above 8.0% are generally regarded as a contraindication due to the increased risk of impaired wound healing, infection, corneal neuropathy, and refractive instability. Preoperative optimization of glycemic control and documentation of stability over several months are therefore essential prior to considering refractive surgery in patients with diabetes[29,43,50]. Although several authors propose an HbA1c threshold of ≤ 7% for refractive surgery, this cut-off is derived from general surgical risk data rather than refractive-specific outcomes. Consequently, HbA1c should be interpreted in conjunction with disease duration, neuropathy, ocular surface status, and retinopathy stage rather than as an isolated criterion[43,50]. LASIK is more commonly indicated than PRK in diabetics, as the healing process is faster in the former compared to the latter. In PRK, the corneal stroma is exposed for a longer duration in the postoperative period, which can predispose to various complications[51]. The use of topical anesthetics should be avoided for 1 week pre-surgery, as their use can increase the fragility of the corneal epithelium. Excessive irrigation of the stromal bed should be avoided during the procedure, and the instillation of sodium hyaluronate drops should be done after flap repositioning[52]. Femtosecond LASIK should be preferred over microkeratome-assisted LASIK, as the former creates a cleaner corneal flap, whereas the latter results in more epithelial complications due to the shearing stress generated from the oscillations of the microkeratome, thereby disrupting the epithelial-basement membrane adherence[53,54]. Flap thickness is more predictable with femtosecond laser–assisted LASIK compared to microkeratome-assisted LASIK, which is associated with greater variability[55,56]. Several studies have demonstrated higher levels of induced spherical and higher-order aberrations following microkeratome-assisted LASIK than femtosecond LASIK[57-59]. Dry eye remains a common postoperative concern; however, studies have shown no significant difference in Ocular Surface Disease Index scores between the two techniques, with values returning to preoperative levels within one month after surgery. Tear film break-up time has been reported to be better preserved in the femtosecond group, likely due to the creation of more uniform and thinner flaps. Contrast sensitivity has also been shown to be superior following femtosecond LASIK[60]. Despite these differences, refractive outcomes are comparable between the two techniques at six months of follow-up[60,61]. Table 1 summarizes the various aspects to look for when planning keratorefractive surgery in diabetic patients[50].

Table 1 Preoperative evaluation in keratorefractive surgery in diabetic patients.

History
Detailed diabetic history	Onset, progression, medication regimen, and altered sensations in the lower extremities
Ocular history	Variations in visual acuity, chronic or recurrent infections, corneal erosions, and dry eye on waking up
Physical examination	Microfilament exam to rule out neuropathy, examination of the foot for ulcer
Slit-lamp examination	Periorbita, tear function, cornea, corneal sensations/esthesiometry, basement membrane health, posterior segment examination
Laboratory investigations	Fasting serum glucose: 130 mg/dL, glycated haemoglobin ≤ 7.9%, Urinalysis: Optional

MANAGING ANTERIOR SEGMENT COMPLICATIONS IN DM

Table 2 depicts various drugs and molecules that are helpful in the management of diabetic keratopathy[9].

Table 2 Various drugs and molecules used in the management of diabetic keratopathy.

Drug	Indication and action
Topical autologous serum	Promotes corneal wound healing
Topical thymosin β4	Non-healing epithelial defect
Topical insulin	Prevents loss of sub-basal nerve plexus. Quicker re-epithelialization after epithelial scraping for vitreoretinal surgeries promotes wound healing
Topical CT-112	Reduction in corneal barrier effect
Injection of insulin-like growth factor-1	Prevention of stem cell loss and improvement of sub-basal nerve plexus density
Topical ranirestat	Promote wound healing, control the expression of matrix metalloproteinases-10, and integrin α3 expression
Nateglinide and glibenclamide	Inhibit Descemet’s membrane changes
Topical naltrexone	Normalize corneal epithelial wound healing, tear film, and corneal sensations
Topical nerve growth factor	Reduced apoptosis and inflammation
Ciliary neurotrophic factor	Improve epithelial stem cells, increase nerve density, and promote epithelial healing
Substance P	Improved wound healing, reinnervation, and reactivation of epidermal growth factor receptor/AKT signaling
Interleukin-1 antagonists	Reduced apoptosis, faster wound healing, sensory stimulation, improved AKT signaling

AKT: Protein kinase B.

CATARACT SURGERY IN DIABETICS

Pathophysiological changes in diabetic cataract

Cataracts in diabetes occur due to the interplay of various mechanisms, including the polyol pathway, autoimmunity, and oxidative and osmotic damage. They ultimately result in the accumulation of sorbitol, AGEs, lens hydration, and oxidative damage due to free radical generation, which leads to lens fiber damage and cataracts. Snowflake cataract is commonly seen in T1DM[62-64].

Timing of surgery

Early surgery for diabetic cataracts is preferred to improve visual outcomes. Cataract surgery should be done before lens opacification occurs to such an extent that it limits fundus evaluation to assess diabetic macular edema (DME). This improves the chances of managing DME to have the best visual outcomes for the patient[65,66].

Preoperative assessment

Blood sugars should be controlled, with no evidence of periocular or ocular infections. A detailed examination, including visual acuity, intraocular pressure, a slit-lamp examination for comprehensive anterior and posterior segment assessments, and gonioscopy, is essential. Other tests, such as B-scan ultrasonography and optical coherence tomography, may be needed in a few cases. Pre-existing proliferative DR should be treated with pan-retinal photocoagulation[67]. Preoperative use of nonsteroidal antiinflammatory drugs reduces the risk of postoperative DME[68]. For pre-existing DME, intraoperative intravitreal injection of a dexamethasone implant is helpful, as it requires less repeatability due to the longer duration of action[69].

Intraocular lens power calculations

Changes in blood sugar levels can affect the intraocular lens (IOL) power calculations due to corneal topographic changes. To achieve the target refraction in diabetic cataract surgery, IOL power calculation should be performed using optical biometry, incorporating the posterior corneal diameter. The use of contact lenses should be discontinued for 2-4 weeks, depending on the material, before IOL power calculations are performed[70,71]. Challenges in IOL power calculations may arise in diabetics who have previously undergone refractive surgery due to the tendency towards hyperopic shift and due to vitreoretinal interface abnormalities or retinal detachment. Such patients need to be counselled, as they may not get the desired and intended correction post-surgery and may require IOL exchange later[72].

Intraoperative considerations

Phacoemulsification with IOL is preferred for better visual outcomes and minimal inflammation[73]. A larger capsulorhexis is preferred, but it should be smaller than the IOL optic due to anterior capsular phimosis and to prevent anterior IOL displacement and posterior capsular opacification (PCO)[74,75]. Pupil expansion devices may be required during surgery due to poor pupillary dilatation[76].

Choice of IOL

Large-diameter hydrophobic IOLs should be preferred for peripheral retinal visualization and to prevent PCO formation. Multifocal, accommodative, and iris-claw lenses should be avoided. A square-edge design is preferred, as the sharp posterior edge adheres to the capsule and prevents the migration of lens epithelial cells and the formation of PCO[77]. IOL implantation in the capsular bag is preferred; however, in cases of posterior capsular rupture, a three-piece IOL can be implanted in the ciliary sulcus with optic capture, which prevents anterior displacement of the IOL. It is preferred to put an IOL in such patients, as they are poor candidates for aphakic contact lens correction for a longer duration[78,79].

Visual prognostication

Cataract surgery in people with diabetes typically yields good visual outcomes, provided the patient maintains good glycemic control and has no other ocular morbidities. The overall result depends on the stage of retinopathy, macular perfusion, and the presence of macular edema[80,81]. Preservative-free eye drops should be used post-surgery to prevent epithelial insult and abnormalities. Endophthalmitis is also a significant concern in such patients, which warrants strict preoperative glycemic control, treatment of any ocular or periocular infections, use of povidone-iodine (5%) in the conjunctival sac preoperatively, and intracameral use of preservative-free moxifloxacin[82].

Other refractive procedures, such as implantable collamer lens and refractive lens exchange, are useful for individuals with very high myopia (Figure 3). Since these procedures require entering the eye and manipulating the anterior chamber, they can have complications such as cataracts, endophthalmitis, and retinal detachment. Strict glycemic control is necessary in cases where these procedures are performed on diabetics.

Figure 3 A toric implantable collamer lens in situ with a central hole in a high myope patient.

CONCLUSION

Refractive surgery in diabetics poses a challenging management dilemma for clinicians due to the potential epithelial healing issues that may arise in the postoperative period, as well as the FDA and American Academy of Ophthalmology listing DM as a relative contraindication for LASIK and PRK. To conclude, no diabetic patient is an ideal candidate for refractive surgery; however, it may be undertaken in patients who have good glycemic control and the surgeon performs a proper and detailed preoperative ocular and systemic assessment. Proper patient counselling and the need for regular postoperative visits to look for and manage various ocular issues can help in achieving the best visual outcomes for the patient. DM should no longer be viewed under the umbrella of contraindication but rather as a spectrum of risk. With appropriate systemic control, ocular screening, and individualized procedure selection, refractive surgery can be safely offered to selected diabetic patients. Future prospective studies are needed to define evidence-based thresholds for glycemic control, corneal nerve density, and biomechanical parameters to further refine patient selection.