Recent developments in cataract surgery.

As guest editor of this special series of the Annals of Translational Medicine (ATM), I would like to share with the readers at large the contributions from invited authors who provided their unique and expert perspectives on the important and critical topics of this focus series titled “Recent Developments in Cataract Surgery”.

Cataract surgery is the most common surgical procedure performed in medicine. Over 20 million surgeries were carried out worldwide in the 2015, including 3.6 million in the United States of America and 4.2 million in the European Union (1). The technology progress enabled cataract surgery to become the safest and most predictable eye surgery. However, the increase in life expectancy and quality of life result in rise expectations regarding the outcomes. Presently, individuals over 70 years of age still wish to maintain an active lifestyle, including driving a car and often performing sports. Cataract surgery is no longer a procedure to eliminate the obstacle in vision providing some restoration of vision. It became a refractive procedure to eliminate all refractive errors, including astigmatism, but also in many cases managing co-existing presbyopia. Thus, this is a field of many new ideas and new developments. We still can be better and there is a demand for techniques that are even more perfect. Longer life span brings some new encounters, including more surgeries performed on patients with dementia and other comorbidities related with ageing, including glaucoma and retinal disorders. Moreover, the anticipated duration of intraocular lens (IOL) in the eye has significantly increased, thus physicochemical properties and IOL endurance should allow the IOL to keep its optical properties for up to three decades.

Congenital cataract is the leading cause of preventable blindness in children (2). Early surgical intervention may prevent deprivation amblyopia and result in good visual prognosis (3). Optimal surgical management includes microincision cataract aspiration combined with posterior capsulotomy, anterior vitrectomy and primary intraocular lens (IOL) implantation (4). Primary IOL implantation is usually performed in children older than 2 years of age. IOL implantation in children younger than 2 years of age remains a matter of controversy (5). The review by Bremond-Gignac and colleagues discusses recent developments in the diagnosis and management of congenital cataract.

It is well known that postoperative intraocular inflammation is usually more severe in younger children and it might be explained by an immature blood-ocular barrier and an underdeveloped immunosuppressive microenvironment or anterior chamber associated immune deviation (6,7). Proper understanding of these mechanisms is pivotal for optimal management of inflammatory response to surgical stimuli (8,9). Postoperative complications arising from intense inflammation include formation of posterior synechiae, posterior capsule opacifications, and fibrous pupillary membrane. This, reinforced anti-inflammatory medication has become the mainstay of pediatric cataract surgery (10). The study by Lai et al. presents developmental characteristics of the cytokine profile in aqueous humor and its relationship with the inflammatory response in children.

The crystalline lens in humans is characterized by life-long growth and regenerative potential what is derived from the its embryonic origin, the epidermis ectoderm, known for the ability to regenerate after injury (11). Lens epithelial cells (LEC) can proliferate and differentiate to achieve certain extent of lens regeneration, what is regulated by a variety of molecular signals and their interactions. It can be hypothesized that modifying the molecular environment can accelerate and improve the optical quality of lens regeneration. Thus, lens regeneration might be a potential option for visual function restoration after cataract surgery (12). It was argued that integrity of lens capsule, LECs and stem cells are prerequisites for functional in situ regeneration. Thus, a novel surgical strategy, minimally invasive lens-content removal surgery, was introduced (13). It included the 1–1.5 mm capsulorhexis opening located in the periphery of the anterior capsule of the lens (13). The review by Liu et al. provides an extensive update on lens regeneration in humans.

Age-related macular degeneration (AMD) is a leading cause of visual impairment in developed countries and a common ocular comorbidity in patients undergoing cataract surgery (14). Although AMD is related with inferior outcomes concerning visual acuity and patient satisfaction (15,16), it generally accepted that patients with AMD benefit from cataract surgery in terms of VA and vision-related quality of life (17). The study by Taipale et al. reports effects of cataract surgery on quality of life for patients with severe vision impairment due to AMD.

Moreover, intraocular magnifying devices recently developed can further increase the quality of vision in this group of patients (18). Implantable Miniature Telescope is the only approved surgical device in the US and can provide central vision magnification at the cost of losing peripheral vision. Meanwhile, the incision size is 7.0–7.5 mm and postoperative astigmatism might be an issue. IOL-VIP System and EyeMax Mono involve a smaller incision and are suitable for both phakic and pseudophakic eyes with similar magnification. The interesting development about EyeMax Mono was to provide a high-quality image in all areas of the macular extending up to 10° from the fovea in case of preferred retina location changes or AMD progression (19). Recently, a prospective multicenter clinical trial about the Scharioth macula lens (SML) in previous pseudophakic eyes with AMD was published (20). Although the SML does not offer distance magnification, it can magnify 2× for objects in a range of 10–15 cm from the eye and can be implanted through 2.2 mm incision with a reduction of postoperative astigmatism. The review by Grzybowski et al. provide an in-depth analysis of different intraocular vision-improving devices in AMD.

Refraction outcome after cataract surgery depends on the precision of pre-operative measurements and calculation formulas used. The most recent formulas use new approaches, including artificial intelligence or ray-tracing analysis. Ray-tracing is method for calculation of every single ray passing through the optical system, and the refraction of rays at each optical surface is calculated using Snell’s law. A map of corneal power achieved in topography or tomography can be transformed into an array of individual measurements representing a polygonal shape. Ray-tracing is employed to analyze the optical properties of every element of the eye in order to establish the performance of the entire optical system. In recent years new formulas were designed to improve the accuracy of refractive predictions, including Barrett Universal II formula, Emmetropia Verifying Optical (EVO) Formula, Kane Formula, Ladas Super Formula, Næser 2 formula, Olsen Formula, Panacea, Pearl DGS, RBF Calculator, T2 Formula, and VRF formula (21-26). The review by Savini et al. discusses recent developments in intraocular lens power calculation methods.

Although surgery is currently the only effective treatment for cataracts, the high cost and technical requirements limit its availability, especially in areas where financial resources and medical facilities are limited (27,28). Thus, pharmacological therapy might become an attractive option when available. Some recent studies have reported several compounds that could prevent and dissolve protein aggregates in the lens, offering a novel anti-cataract drug screening strategy (29,30). The review by Xu et al. presents the advances in pharmacotherapy of cataracts.

One strategy to improve the outcomes after cataract surgery is to decrease the rate of peri-operative complications. It was shown that some conditions had been related with increased risk of perioperative complications, including pseudoexfoliation (PXF) and zonular weakness, use of α1-blockers, dense cataracts and poor mydriasis (31). Moreover, the level of surgeons’ experience and annual operation volume were recognized as factors correlating with the frequency of cataract surgery adverse events. Posterior capsule rupture, in turn, was associated with 42-fold risk for retinal detachment and 8-fold risk for endophthalmitis within 3 months after cataract surgery (32). It was recently showed that the New Zealand Cataract Risk Stratification (NZCRS) scoring system, that aided in identification of higher-risk cataract cases and appropriate case-to-surgeon allocation was associated with a 40% reduction in intraoperative complications (33). Thus, preoperative risk stratification seems to be an important tool to reduce intraoperative phacoemulsification complications. The study by Aaronson et al. presents an analysis of adverse effects among 14,520 eyes in relation to surgical experience.

Numerous studies have related the use of α1 adrenoceptor antagonists, especially tamsulosin, with the occurrence of intraoperative floppy iris syndrome (IFIS) (34). This group of drugs is used commonly in the treatment of benign prostate hypertrophy and systemic hypertension, both diseases typical for people aged over 70 years. The occurrence of IFIS might be accompanied by increased rates of multiple complications, including corneal endothelial loss, iris trauma, anterior capsule tears, posterior capsule rupture, retained nuclear fragments, vitreous loss, macular edema and postoperative ocular inflammation (35). Discontinuation of α1 adrenoceptor antagonists before cataract surgery can neither prevent the occurrence of IFIS nor improve the severity of IFIS (36). American Urological Association recommends that urologists avoid using tamsulosin when their patients are likely to receive cataract surgery in the near future (37). A review by Yang et al. provides an update on intraoperative floppy iris syndrome, including its pathogenesis, risk factors and management.

Endophthalmitis is a significant complication of cataract surgery, limiting the visual potential of the eye with the incidence from 0.03% to 0.7% (38). Risk factors for endophthalmitis include surgical complications (wound leak, posterior capsule rupture, vitreous loss or zonular complications), silicone IOL, clear corneal incision, age over 85 years, uncontrolled blepharitis or other ocular surface disease, diabetes mellitus, an immunocompromised state, infectious foci near the surgical site, early wound leak and no use of intracameral antibiotic. Preoperative antisepsis with povidone-iodine (PVI) significantly decreases the rate of bacterial endophthalmitis and is a worldwide accepted strategy (39). Moreover, dilute PVI solution has an excellent safety profile, and significantly reduces the anterior chamber contamination rate after cataract surgery (40). Interestingly, a systematic review and meta-analysis failed to find any evidence supporting the use of postoperative topical antibiotics after ocular surgery (41). The review by Sengillo et al. presents the update on the prophylaxis of postoperative Endophthalmitis and Toxic Anterior Segment Syndrome.

IOLs due to its biomaterial characteristics are prone after intraocular implantation to physico-chemical processes leading is some cases to opacification formation (42,43). The hydrophobic acrylic lenses have been reported to show microvacualisation often also named as glistenings, while calcifications develop more often in hydrophilic acrylic lenses. With the prolonged expected time of IOL duration within human eye its long-term optical quality is of critical importance. Although majority of the peer-reviewed studies did not show a significant impact of glistenings and subsurface nanoglistenings on visual acuity, there are recent data about its significant effect on straylight (42,44,45). Increased straylight can result in disability glare, hazy vision, and loss of contrast (46). Since straylight is not measured in standard clinical conditions, it might be easily overlooked. Thus, this area should be studied in detail in future. Moreover, since calcifications in hydrophilic materials affect visual function relatively easily, it is probably not preferable to use hydrophilic materials for IOL until the mechanism of calcification and the preventive method are elucidated. The review by Grzybowski et al. provides the updated analysis on intraocular lens opacifications and their impact on vision quality.

In recent years, lens extraction has been shown to lower the intraocular pressure (IOP) and reduce the need of IOP-lowering medications in different types of primary glaucoma, especially in narrow angle glaucoma. The lens in these cases is usually abnormally thick and anteriorly positioned, thus its removal helps opening up the closed angle. It was shown that phacoemulsification alone leads to opening of the drainage angle and deepening of the anterior chamber (47), reducing the need of further glaucoma surgery. Thus, for patients with primary open glaucoma and cataract, phacoemulsification with or without combined trabeculectomy is a standard surgical option. Although the standard use of clear lens extraction in these patients is much more controversial, the EAGLE Study showed its benefits and effectiveness when compared to laser peripheral iridotomy in controlling IOP without significant increase in risks and complications (48). The review by Tsui et al. discuss the role of lens extraction in glaucoma management.

Simultaneous bilateral cataract surgery (SBCS), introduced over 60 years ago, and initially reserved to some specific indications, including eye camps and general anesthesia surgery, gained recently increasing interest. The major historical concerns against SBCS, namely the risk of bilateral endophthalmitis and the risk of postoperative refractive error, are much less limiting today (49). With the present peri-operative antiseptic policy, including the use the intracameral antibiotic and separating completely each eye surgery the risk of bilateral endophthalmitis is extremely low (50). The postoperative refractive error can be prevented by following carefully the inclusion criteria for SBCS. On the other hand, advantages of SBCS include restoring binocularity and stereopsis faster, particularly important in patients with multifocal IOLs. It should be highlighted here that corneal refractive surgeries and intravitreal injections are conducted today as standard bilateral simultaneous procedures. Moreover, SBCS is the preferred surgical approach during COVID epidemic, decreasing significantly the number of contacts between patient and medical center. The review by Singh et al. presents the evolution and recent developments in SBCS.

Living in present time, we are often oriented to the future, not to the past. Interestingly there are still many historical ophthalmic enigmas. The oldest known description of cataract surgery by Greek philosopher Chrysippus was recently described, however, the origin of cataract surgery is still mysterious (51). It was performed in ancient India, and generally it is believed that it was conducted by Sushruta around 600 BC (52), although documented source comes from the 9th century CE and were not analyzed in detail before. The review by Leffler et al. provides in-depth analysis of original Sanskrit and ancient Greek texts to reveal the unknown aspects of early cataract surgery in ancient India and ancient Greece. It provides also overview of the existing knowledge from earliest known descriptions to phacoemulsification.

Andrzej Grzybowski

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