Advancements in keratoplasty: Exploring newer techniques and imaging modalities for enhanced surgical outcomes

Abstract

Keratoplasty, the transplantation of corneal tissue, is a well-established surgical procedure for the treatment of various corneal diseases. Over the years, advancements in keratoplasty techniques have significantly improved surgical outcomes and patient satisfaction. This review article provides an overview of newer techniques and imaging modalities in keratoplasty that have emerged as promising options for corneal transplantation. The article begins with a brief overview of traditional keratoplasty techniques, including penetrating keratoplasty, deep anterior lamellar keratoplasty, Descemet’s stripping automated endothelial keratoplasty (EK), and Descemet’s membrane EK. It then delves into the discussion of newer techniques, including femtosecond laser-assisted keratoplasty, Bowman layer transplantation, and the role of anterior segment optical coherence tomography in keratoplasty. This review article aims to provide ophthalmologists with a comprehensive understanding of the newer techniques in keratoplasty, their advantages, limitations, and clinical outcomes. It emphasizes the importance of individualized treatment planning, considering patient-specific factors, and utilizing advanced imaging modalities to optimize surgical outcomes. The incorporation of newer techniques and imaging modalities in keratoplasty has the potential to revolutionize the field, offering improved visual outcomes, reduced complications, and enhanced patient satisfaction. Continued research and technological advancements will further refine these techniques, paving the way for the future of keratoplasty and improving the quality of life for patients with corneal diseases. We evaluate the currently available literature in this article to provide a comprehensive overview of contemporary surgical and imaging methods in ophthalmology to facilitate additional developments in the field of corneal transplantation.

INTRODUCTION

Keratoplasty, also known as corneal transplantation, is a surgical procedure that replaces a damaged or diseased cornea with a healthy cornea from a donor.[1] The cornea plays a crucial role in focusing light onto the retina, enabling clear vision. However, various conditions such as corneal scars, infections, dystrophies, and degenerations can lead to significant visual impairment or blindness.[2] Keratoplasty is vital for restoring visual acuity and improving the quality of life for patients with corneal diseases.[3] According to the World Health Organization, corneal diseases are responsible for approximately 5% of global blindness cases.[4] Keratoplasty offers a viable treatment option for patients with corneal pathologies that cannot be managed effectively through nonsurgical interventions.[5] Keratoplasty aims to restore corneal integrity, visual function, and overall ocular health.[6]

Keratoplasty has undergone remarkable advancements since its inception in the early 20^th century. The initial technique, known as penetrating keratoplasty (PKP), involved the complete replacement of the cornea. While PKP was successful in restoring vision, it had significant drawbacks, including high rates of graft rejection and induced astigmatism.[7,8]

To address these limitations, newer techniques such as deep anterior lamellar keratoplasty (DALK) and endothelial keratoplasty (EK) were developed. DALK involves the removal of the diseased anterior layers of the cornea while preserving the healthy endothelium, resulting in improved visual outcomes and lower rejection rates compared to PKP.[9] EK, on the other hand, focuses on selectively replacing the diseased endothelial layer, either through Descemet’s stripping automated EK (DSAEK) or Descemet’s membrane EK (DMEK), thus further reducing complications and promoting better visual recovery.[10]

The purpose of this review article is to explore the latest advancements in keratoplasty techniques beyond traditional approaches such as PKP, DALK, DSAEK, and DMEK. The field of corneal transplantation continues to evolve rapidly, with the introduction of innovative surgical techniques and technologies. By focusing on these newer techniques, we aim to provide a comprehensive overview of the current state-of-the-art in keratoplasty, highlighting their advantages, limitations, clinical outcomes, and potential impact on patient care.

In particular, this review article will delve into emerging techniques such as femtosecond laser-assisted keratoplasty (FLAK), which utilizes precise laser technology for enhanced surgical accuracy and improved outcomes. In addition, we will discuss Bowman layer transplantation (BLT), a procedure that targets specific corneal layers for selective replacement, offering potential advantages in certain clinical scenarios. Furthermore, we will explore the role of anterior segment optical coherence tomography (AS-OCT) in preoperative evaluation, intraoperative guidance, and postoperative assessment, which has significantly contributed to the refinement of keratoplasty procedures.

By critically evaluating these newer techniques, their comparative effectiveness, and potential future directions, this review article aims to provide clinicians and researchers with a comprehensive understanding of the evolving landscape of keratoplasty. Ultimately, the knowledge gained from this review will contribute to optimizing patient outcomes, expanding treatment options, and paving the way for further advancements in the field of corneal transplantation.

TRADITIONAL KERATOPLASTY TECHNIQUES

Penetrating keratoplasty

PKP has been the gold standard for corneal transplantation. It involves the full-thickness replacement of the recipient’s cornea with a donor cornea.[11,12] The procedure begins with the removal of the central corneal button from the recipient’s cornea, followed by suturing the donor cornea in place. It has demonstrated good visual outcomes and graft survival rates in many cases.[13] However, PKP is associated with several limitations and potential complications. These include prolonged visual recovery, irregular astigmatism, suture-related issues, and the risk of graft rejection. In addition, the need for full-thickness corneal transplantation results in a higher risk of endothelial cell loss and secondary glaucoma.[14,15] Despite its drawbacks, PKP remains a valuable technique in specific cases where full-thickness corneal replacement is warranted.

Deep anterior lamellar keratoplasty

DALK is a partial-thickness corneal transplantation technique that selectively replaces the anterior layers of the cornea while preserving the recipient’s healthy endothelium.[16] It is primarily indicated for corneal stromal diseases, such as keratoconus and corneal scars, where the endothelium remains functional. DALK offers advantages over PKP by reducing the risk of endothelial rejection and graft failure.[17] The procedure involves the creation of a deep stromal dissection, separating the diseased anterior corneal layers from the healthy endothelium. The donor cornea’s anterior layers are then sutured into place. DALK provides better visual outcomes, faster visual recovery, and reduced risk of graft rejection compared to PKP.[18] However, it is technically challenging and requires expertise in achieving a complete stromal dissection without damaging the Descemet’s membrane.

Descemet’s stripping automated endothelial keratoplasty

DSAEK is a posterior lamellar keratoplasty technique that specifically targets corneal endothelial dysfunction. It involves replacing the recipient’s diseased or dysfunctional endothelium with a thin donor corneal graft consisting of the Descemet’s membrane and endothelium. The procedure begins with the creation of a partial-thickness stromal pocket or tunnel in the recipient cornea. The donor cornea is prepared by manual or automated stripping the Descemet’s membrane and endothelium, which is then inserted into the recipient’s eye through the prepared tunnel.[19] The graft is held in place using an air or fluid bubble. DSAEK offers advantages over PKP by preserving the recipient’s anterior corneal integrity, resulting in faster visual recovery and reduced astigmatism. DSAEK has become a popular choice for treating corneal endothelial dysfunction, including conditions such as Fuchs’ endothelial corneal dystrophy and pseudophakic bullous keratopathy. It has shown excellent graft survival rates and improved visual outcomes.[20] However, DSAEK is associated with potential complications, such as graft dislocation, interface haze, and endothelial cell loss.[21,22] Advances in instrumentation and surgical techniques, such as precut donor grafts and the use of femtosecond lasers, have further refined DSAEK and improved surgical outcomes.[23]

Descemet’s membrane endothelial keratoplasty

DMEK is a newer technique that involves the transplantation of the donor’s Descemet’s membrane and endothelium without any stromal tissue.[24] It is the most anatomically accurate method of replacing dysfunctional corneal endothelium. The procedure begins by preparing the donor cornea, carefully stripping the Descemet’s membrane along with the endothelium. The Descemet’s membrane graft is then delicately inserted into the recipient’s eye, positioning it with an air or gas bubble. DMEK offers several advantages, including rapid visual recovery, improved visual acuity, reduced astigmatism, and lower risk of graft rejection.[25]

Advantages over Descemet’s stripping automated endothelial keratoplasty

DMEK has several advantages over DSAEK. By transplanting only the Descemet’s membrane and endothelium, DMEK avoids the introduction of stromal tissue, resulting in better visual outcomes and reduced refractive error. The absence of stromal tissue also decreases the risk of graft rejection and immune-mediated complications. DMEK provides a smoother graft interface, leading to improved visual quality and contrast sensitivity.[10,26]

Challenges and complications

Despite its advantages, DMEK presents unique challenges. The delicate nature of the Descemet’s membrane graft requires meticulous handling and surgical expertise. The graft preparation and unfolding process can be technically demanding, necessitating careful surgical techniques and appropriate training. Complications associated with DMEK include graft detachment, graft dislocation, and prolonged air or gas tamponade.

Clinical outcomes and future directions

DMEK has shown excellent clinical outcomes, with high graft survival rates and improved visual acuity compared to previous techniques.[27] Ongoing research aims to refine surgical techniques, develop standardized protocols, and optimize graft preparation and handling methods. Advancements in imaging technology, such as AS-OCT, facilitate better visualization of graft adherence and identification of complications. The future of DMEK lies in continued refinement of surgical techniques, graft preparation methods, and postoperative management. Further studies are needed to evaluate long-term graft survival rates, the impact of donor age and quality on outcomes, and the optimal patient selection criteria. In addition, investigations into tissue engineering, bioengineered scaffolds, and regenerative medicine hold promise for developing alternative approaches to EK.

DMEK represents a significant advancement in corneal transplantation techniques. It offers improved visual outcomes, faster visual recovery, and reduced risk of graft rejection compared to DSAEK. While challenges exist, ongoing research and technological advancements continue to refine and expand the applications of DMEK. With further developments, DMEK has the potential to become the standard of care for corneal endothelial dysfunction, providing patients with improved visual outcomes and quality of life.

NEWER TECHNIQUES IN KERATOPLASTY

Femtosecond laser-assisted keratoplasty

FLAK is an innovative approach that utilizes femtosecond laser technology to perform precise corneal incisions and graft preparation.[28] FLAK offers several advantages over traditional keratoplasty techniques, revolutionizing the field of corneal transplantation.

Procedure and advantages

FLAK involves the use of a femtosecond laser to create donor and recipient corneal incisions with micron-level precision. The laser enables customization of incision depth, shape, and configuration according to the patient’s specific needs. The donor cornea is prepared by creating an accurate trephination of the tissue, resulting in a well-fitting graft. The recipient cornea is also precisely incised, facilitating seamless graft integration.

The advantages of FLAK include:

• Enhanced safety: The femtosecond laser enables precise and controlled incisions, minimizing the risk of complications such as wound leaks and induced astigmatism.[29] In addition, the noncontact nature of the laser reduces the risk of infection and tissue trauma

• Customization: FLAK allows customization of the graft size, shape, and depth, tailored to the patient’s individual requirements. This customization improves graft–host matching and can optimize visual outcomes[30]

• Faster visual rehabilitation: FLAK’s accurate incisions promote rapid wound healing and faster visual recovery compared to traditional techniques. Patients often experience improved visual acuity in a shorter period.

Comparisons with traditional techniques

Compared to traditional keratoplasty techniques such as PKP and DSAEK, FLAK offers distinct advantages:

• Precise incisions: FLAK utilizes femtosecond laser technology, enabling precise and reproducible corneal incisions, resulting in improved wound architecture and reduced induced astigmatism.

• Enhanced graft–host interface: The customization of graft and recipient bed incisions allows for a precise and secure graft–host interface, leading to improved graft survival rates and visual outcomes

• Reduced surgical trauma: FLAK reduces surgical trauma due to the noncontact nature of the femtosecond laser, minimizing tissue manipulation and reducing the risk of endothelial cell loss.[31]

Clinical outcomes and considerations

Studies evaluating FLAK have reported encouraging clinical outcomes. Improved refractive outcomes, including reduced astigmatism and improved uncorrected visual acuity, have been observed. The precise graft–host interface achieved with FLAK has contributed to better graft survival rates compared to traditional techniques.[32,33] Considerations for FLAK include the initial investment cost of the femtosecond laser system and the need for specialized training in laser-assisted corneal surgery. Surgeons must familiarize themselves with the specific laser platform and techniques to ensure safe and effective utilization.

Bowman Layer Transplantation

BLT is an innovative technique that focuses on replacing the Bowman layer (BL), a thin layer of the cornea, to address anterior corneal diseases and irregularities.[34]

BLT is a promising treatment for advanced keratoconus, with a success rate of 84% over 5 years.[35] It has also been used to manage persistent subepithelial haze after excimer laser surface ablation.[36] The procedure has shown to be beneficial in reducing ectasia in advanced keratoconus with minimal complications.[37] The use of a thicker lamellar portion of the anterior cornea, including both BL and anterior stroma, has been suggested to potentially enhance the effectiveness of the procedure.[38] It has been found to be a feasible surgical technique, providing corneal flattening and improving visual acuity,[39] and has also been shown to reduce and stabilize corneal ectasia in eyes with progressive, advanced keratoconus.[40]

Procedure and applications

BLT involves the transplantation of a thin BL graft obtained from a donor cornea to restore the integrity and smoothness of the anterior cornea. The graft is meticulously prepared and transplanted onto the recipient cornea, with the aim of improving corneal surface regularity, addressing anterior corneal dystrophies, and managing irregular astigmatism.

BM transplantation may be done in two ways:

1. BL “inlay” technique: It involves implanting isolated donor BL grafts into manually dissected, mid-stromal pockets in recipient corneas. In order to flatten and stabilize progressive, keratoconus with little risk of problems, isolated BL inlay grafting would be a good choice[41]

2. BL “onlay” technique: A theoretical argument against mid-stromal BL “inlay” grafting is that it positions the donor tissue in a nonanatomic site that would be less ideal than a more subepithelial, natural location. In onlay procedure, the recipient’s corneal epithelium is removed, and an isolated BL graft is just placed into the recipient’s anterior corneal stroma and given time to “dry in.” By allowing the BL graft to “stick” to the recipient cornea’s surface, drying may eliminate the need for glue or sutures during fixation and bandage contact lens is placed over the cornea.[42]

BLT has applications in various corneal conditions, postrefractive corneal haze, postherpetic scarring, keratoconus, anterior basement membrane dystrophy, Salzmann’s nodular degeneration, and irregular astigmatism secondary to corneal trauma or refractive surgery.[43]

Advantages and limitations

Advantages of BLT include:

• Targeted treatment: BLT specifically addresses anterior corneal pathologies, allowing for a more precise and localized intervention

• Reduced invasiveness: BLT is a minimally invasive procedure, as it involves the transplantation of only the BL without disturbing the deeper corneal layers. This reduces the risk of endothelial cell loss and preserves corneal biomechanical stability[44]

• Improved corneal surface regularity: BLT can lead to smoother and more regular corneal surfaces, resulting in improved visual outcomes and reduced higher-order aberrations.

Limitations of BLT include:

• Limited indications: BLT is primarily suitable for anterior corneal diseases that predominantly involve the BL. It may not be applicable for conditions that affect deeper corneal layers or endothelial dysfunction[45]

• Long-term outcomes: Long-term studies on the durability and stability of BLT are limited, and further research is needed to assess its long-term efficacy.[46] Table 1 shows the specifics of a few research on BLT’s influence on outcome measured and intervention effect.

Table 1.

Specifics of a few research on Bowman layer transplantation’s influence on outcome measured and intervention effect

Study	Study design	Length of follow-up	Participant count	Intervention	Outcome measured	Intervention effect
van Dijk et al., 2015[40]	Prospective, nonrandomized, cohort study	Up to 36 months	19	Mid-stromal isolated BLT for progressive advanced keratoconus	BSCVA BCLVA Scheimpflug-based corneal tomography measurements Endothelial cell density Biomicroscopy Refraction Intraoperative and postoperative complications	At 1 month following surgery, the average maximum keratometry dropped from 77.2±6.2 diopters 69.2±3.7 diopters (P<0.001) and then stabilized (P≥0.072). After surgery, the mean BSCVA showed significant improvement (P<0.001), going from 1.27±0.44 logarithm of the minimum angle of resolution units before surgery to 0.90±0.30 logarithm of the minimum angle of resolution units 12 months later (P=0.105). In contrast, the mean BCLVA barely changed. There was no change in endothelial cell density (P=0.355), but mean thinnest-point pachymetry rose from 332±59 µm before surgery to 360±50 µm at the most recent follow-up (P=0.012)
van Dijk et al., 2018[45]	Prospective, single-center, interventional case series	5 years	20	Isolated BLT for advanced keratoconus	Simulated and maximum keratometry (Kmean and Kmax) values BSCVA BCLVA Endothelial cell density Complications Densitometry values	After a first decline from pre- to 1 month postoperatively (P<0.001 each), Kmean and Kmax values were steady for up to 5 years following surgery (P=0.310 and P=0.195 for 5 years compared to 1 month follow-up, respectively). Once there was an initial improvement from pre- to 12 months postoperatively (P=0.007), the mean LogMAR BSCVA remained steady (P>0.99). Between preoperative and five years postoperative, the mean BCLVA remained unchanged (P=0.219). The mean densitometry values were higher than preoperatively for all postoperative follow-ups (P<0.001). 5 years after surgery, an estimated 84% of cases were successful, according to Kaplan–Meier analysis. From before surgery to 5 years after it, endothelial cell density did not change (P=0.319)
Oganesyan et al., 2019[47]	A case series study	26±6.0 months	30	BLT for progressive keratoconus stages III–IV	Kmax CTP values Visual acuity in scleral contact lenses ECD Depth of graft location	Kmax decreased by an average of 0.6±0.5 diopter, TTR increased by an average of 36.7±13.9 µm, visual acuity without correction improved in 4 patients from 0.03±0.04 to 0.08±0.01
Parker et al., 2020[48]	Case report	12 months	1	BLT with an onlay grafting (after previous radial keratotomy)	BSCVA Scheimpflug-based corneal tomography AS-OCT	On a scale of 1–10, the subjective complaints of visual fluctuation decreased after surgery, from 10 to 3. The BSCVA did not alter from the preoperative to the postoperative state (20/40; 0.5). A 5.9 diopter total center corneal steepening was seen on corneal tomography. A fully epithelialized and well-integrated graft was revealed by biomicroscopy, Scheimpflug imaging, and AS-OCT; a few small epithelial remnants were seen in the previous keratotomy incisions
Dapena et al., 2020[49]	Case series	18 months	2	BLT with onlay for herpes corneal scars	BSCVA BCLVA Biomicroscopy Scheimpflug-based corneal tomography measurements AS-OCT	Case 1: BCLVA with scleral lens improved from 20/100 (0.1) postoperatively to 20/32 (0.6) Case 2: BCLVA of 20/36 (0.55) postoperatively Biomicroscopy, imaging, and AS-OCT findings revealed well-integrated and fully epithelialized graft following the surgery
van der Star et al., 2021[50]	Case series	8 years	35	BLT with inlay transplantation for progressive keratoconus	BSCVA BCLVA Scheimpflug-based corneal tomography Simulated keratometry Maximum keratometry Central corneal thickness Thinnest point thickness Complications Success rate	The BSCVA increased for Group 1 (P=0.03), but the mean logarithm of the lowest angle of resolution best contact lens-corrected visual acuity did not change for the entire group or the two subgroups from preoperative up to the final available follow-up (all P>0.05) While no significant changes were seen in Group 2, all P>0.05, Group 1 revealed an average Kmax drop of 7D in the first month (P<0.001) and no additional changes were seen up to 8 years postoperatively (P>0.05). Four eyes (n=3 Group 1, n=1 Group 2) experienced postoperative KC progression, and one eye (Group 2) required retransplantation due to inadequate visual function. Based on Kaplan–Meier analysis, the projected success rate at the 5–8-year mark was 85%
Mulders-Al-Saady et al., 2022[51]	A case report	1.5 years	1	Bowman layer onlay grafting for recurrent corneal erosions in map-dots- fingerprint dystrophy	Restoration of the corneal surface Absence of complaints Absence of recurrence of the epithelial corneal erosion	The patients experienced no symptoms or recurrence of the epithelial corneal erosion until 1.5 years after surgery, at which point the epithelium above the transplant was smooth
Thiago Barbosa et al., 2022[46]	A single-center retrospective study	13.2±4.9 months	50	Femtosecond laser-assisted BLT	Mean maximum keratometry Mean preoperative best contact lens Corrected visual acuity BCLVA BCLVA loss	At 6 months following surgery, the mean maximum keratometry dropped 1.93 diopter, but the mean preoperative best contact lens corrected visual acuity BCLVA remained unchanged
Oganesyan et al., 2023[52]	Case series	36 months	7	BLT in combined treatment of recurrent pterygium	Refractometry data Visometry data (without correction and with spectacle correction) Optical coherence tomography of the retina Spectacle-corrected visual acuity Topographic astigmatism Recurrence of pterygium Cosmetic outcomes of the treatment	No pterygium recurrences was noted. The average corrected visual acuity with spectacles was 0.86±0.2 diopters, whereas the topographic astigmatism was 1.48±1.4 diopters. Every patient was pleased with how the treatment’s cosmetic results turned out

BSCVA: Best spectacle-corrected visual acuity, CTP: Corneal thinnest point, ECD: Endothelial cell density, BCLVA: Best contact lens-corrected visual acuity, TTR: Time to resolution, AS-OCT: Anterior segment optical coherence tomography, BLT: Bowman layer transplantation

Evidence and future directions

The evidence supporting BLT is still emerging, with ongoing research focused on refining techniques and assessing long-term outcomes. Early studies have demonstrated promising results in terms of improved visual acuity, corneal surface regularity, and patient satisfaction. Future directions include exploring combination therapies, such as combining BLT with other techniques such as FLAK or DMEK, to optimize visual outcomes in complex corneal conditions.

In conclusion, newer techniques in keratoplasty, such as FLAK and BLT, offer innovative approaches to corneal transplantation. FLAK provides advantages in terms of precise incisions, customization, and faster visual rehabilitation compared to traditional techniques. BLT allows targeted treatment of anterior corneal diseases while preserving corneal biomechanics and improving corneal surface regularity. Although further research and long-term studies are needed to fully understand the efficacy and durability of these techniques, they hold significant promise for the future of keratoplasty and have the potential to improve visual outcomes for patients with corneal diseases and irregularities.

ANTERIOR SEGMENT OPTICAL COHERENCE TOMOGRAPHY IN KERATOPLASTY

Role of anterior segment optical coherence tomography in preoperative evaluation

AS-OCT has become an invaluable tool in the preoperative evaluation of patients undergoing keratoplasty.[53] AS-OCT provides high-resolution cross-sectional imaging of the cornea, enabling detailed visualization of corneal layers, thickness measurements, and assessment of corneal pathologies [Figure 1]. The minimum resolution needed for AS-OCT varies depending on the specific application. Li et al.[54] achieved an axial resolution of 10 μm, which is suitable for general anterior segment imaging. The potential for greater-resolution imaging was demonstrated by Asam et al.[55] using spectral-domain OCT with an axial resolution of 6 μm. The importance of high resolution for specific applications such as corneal topography and anterior chamber biometry was emphasized by Hong and Sun.[56] Both Domínguez Vicent et al.[57] and Garcia Marin et al.[58] highlighted the precision and accuracy of high-resolution OCT for anterior segment measurements and tissue segmentation. Therefore, a minimum resolution of 10 μm is generally sufficient for most AS-OCT applications, but higher resolutions may be needed for specific clinical and research purposes.

Figure 1.

Anterior segment optical coherence tomography for normal cornea depicting corneal thickness and all the layers of the cornea. OCT: Optical coherence tomography

Epithelial mapping in AS-OCT offers several advantages, and it provides crucial information for planning and monitoring procedures, such as identifying areas of loose epithelial adherence in recurrent corneal erosion syndrome.[59] The nonuniform epithelial thickness profile can be used for early screening in keratoconus, monitoring for corneal ectasia, and planning hyperopic treatment.[60] Furthermore, it can be used to diagnose irregular astigmatism and plan transepithelial PRK treatment. These applications demonstrate the potential of epithelial mapping in improving the safety and efficacy of corneal refractive surgery.

Corneal topography and pachymetry

AS-OCT provides accurate corneal topography and pachymetry measurements, aiding in the selection of appropriate graft size and shape. This information helps surgeons plan the surgical procedure and determine the optimal location for graft placement.

Evaluation of corneal pathologies

AS-OCT allows for the identification and characterization of various corneal pathologies, such as corneal scars, irregular astigmatism, bullous keratopathy, and corneal dystrophies[61] [Figure 2]. This information helps guide surgical decision-making, including the choice of keratoplasty technique and the assessment of potential graft–host interactions.

Figure 2.

Anterior segment optical coherence tomography of a patient with pseudophakic bullous keratopathy showing increased corneal thickness and bullae, planned for Descemet’s stripping automated endothelial keratoplasty

Assessment of anterior chamber parameters

AS-OCT enables the measurement of anterior chamber depth, angle evaluation, and identification of any associated abnormalities.[62] This information is crucial for assessing the risk of postoperative complications, such as angle-closure glaucoma, and aids in surgical planning.

Intraoperative guidance and monitoring

AS-OCT plays a vital role in providing real-time intraoperative guidance and monitoring during keratoplasty procedures. It allows surgeons to assess the surgical progress, evaluate graft apposition, and ensure optimal placement.[63]

Graft–host interface evaluation

AS-OCT enables surgeons to visualize the graft–host interface during the surgery. It provides real-time feedback on the apposition of the graft to the recipient cornea, allowing for adjustments as needed to ensure proper alignment and adherence.[42,64]

Stromal bed assessment

AS-OCT aids in evaluating the recipient stromal bed’s smoothness and regularity during the procedure. Surgeons can identify any irregularities or gaps and address them accordingly to optimize graft integration.

Intraoperative pachymetry

AS-OCT facilitates intraoperative pachymetry measurements, providing valuable information about the corneal thickness at different stages of the procedure. This allows surgeons to monitor corneal thickness changes and ensure the preservation of adequate corneal thickness postsurgery.[65,66]

Postoperative assessment and follow-up

AS-OCT continues to be a valuable tool in the postoperative assessment and follow-up of patients undergoing keratoplasty. It aids in the evaluation of graft–host integration.

Assessment of graft–host interface

AS-OCT allows for the evaluation of the graft–host interface postoperatively, providing insights into the quality of graft attachment and integration. Surgeons can assess the extent of apposition, identify any areas of separation or irregularities, and make informed decisions regarding postoperative management [Figure 3].

Figure 3.

Anterior segment optical coherence tomography of a patient who underwent manual Descemet Stripping Endothelial Keratoplasty (DSEK) surgery showing good graft–host apposition (postoperative day 1)

Corneal thickness monitoring

AS-OCT facilitates the monitoring of corneal thickness changes following keratoplasty. Serial measurements can help identify any signs of graft edema or rejection and guide therapeutic interventions. Monitoring corneal thickness is particularly crucial in EK techniques such as DSAEK and DMEK, where maintaining optimal corneal thickness is essential for visual outcomes.

Visualization of corneal architecture

AS-OCT allows for the detailed visualization of corneal architecture and helps identify any complications or abnormalities postsurgery. Surgeons can assess the presence of irregular astigmatism, epithelial ingrowth, interface haze, or other factors that may impact visual outcomes. Early detection of these issues enables timely intervention and management.

Evaluation of graft survival

AS-OCT plays a role in assessing graft survival and stability over time. Serial imaging can monitor changes in graft thickness, integrity, and clarity, providing valuable information about the long-term prognosis. Any signs of graft rejection, graft failure, or complications can be detected early, allowing for prompt intervention[66] [Figure 4].

Figure 4.

Anterior segment optical coherence tomography of a patient that underwent penetrating keratoplasty (1 month back) showing signs of graft failure (bullae and graft edema)

Customized treatment planning

AS-OCT provides detailed imaging of the cornea, allowing for customized treatment planning based on individual patient characteristics. By evaluating corneal topography, pachymetry, and other parameters, surgeons can tailor postoperative interventions, such as contact lens fitting or refractive surgeries, to optimize visual outcomes.[67]

In summary, AS-OCT plays a multifaceted role in the management of keratoplasty patients. It assists in the preoperative evaluation, guiding surgical decision-making, and aids in the intraoperative assessment and monitoring of graft apposition and integration. Postoperatively, AS-OCT allows for the evaluation of graft–host interface, corneal thickness, and overall corneal architecture. The ability to visualize and assess these parameters contributes to the accurate diagnosis of complications, timely intervention, and customized treatment planning, ultimately leading to improved outcomes for patients undergoing keratoplasty. With the continuous advancement of technology, ASOCT is anticipated to play an even more significant role in the field of keratoplasty, helping to refine surgical techniques and enhance patient care.

FUTURE PERSPECTIVES AND INNOVATIONS

Artificial corneas and bioengineered constructs

The field of keratoplasty is witnessing exciting developments in the realm of artificial corneas and bioengineered constructs. These innovative approaches aim to overcome the challenges associated with donor tissue shortage and the risk of graft rejection.[68]

Synthetic corneas

Researchers are actively exploring the development of synthetic corneas, also known as keratoprostheses, as an alternative to donor corneal tissue. These prosthetic devices are designed to replace the diseased or damaged cornea and restore visual function.[69] Various materials, such as polymers and ceramics, are being investigated for their biocompatibility and optical properties. The goal is to create a synthetic cornea that can integrate seamlessly with the surrounding ocular tissues and provide excellent visual outcomes.[70]

Bioengineered constructs

Another approach gaining momentum is the development of bioengineered corneal constructs. Scientists are working on creating corneal tissue in the laboratory using tissue engineering techniques. This involves seeding corneal cells onto scaffolds or matrices and allowing them to grow and differentiate into functional corneal tissue.[71] Bioengineered constructs hold great promise as they offer the potential for personalized corneal replacements with reduced risk of graft rejection.

GENE THERAPY IN KERATOPLASTY

Gene therapy has emerged as a revolutionary approach in the treatment of various genetic disorders, and its potential application in keratoplasty is being explored. The time between donor cornea collection and recipient transplant is ideal for applying pretreatment to reduce corneal graft rejection. Ex vivo experiments with rabbit and human donor corneal buttons with adeno-associated virus vector-mediated human leukocyte antigen G showed no edema and neovascularization for over 2.5 months after allotransplantation. Xenotransplantation showed a delayed rejection time from 18 to 29 days.[72]

Targeting corneal dystrophies

Gene therapy holds the potential to deliver therapeutic genes directly to corneal cells, targeting specific genetic mutations responsible for corneal dystrophies. By introducing functional genes, it is possible to correct the underlying genetic defects and halt or reverse the progression of the disease.[73,74] This approach could potentially eliminate the need for corneal transplantation in certain cases.[75,76]

Modulation of wound healing

Gene therapy techniques can also be employed to modulate the wound healing process after keratoplasty. By delivering genes that promote corneal epithelial migration, stromal remodeling, or inhibition of fibrosis, it may be possible to enhance the healing response and improve visual outcomes following surgery.[77]

NANOTECHNOLOGY AND DRUG DELIVERY SYSTEMS

The field of nanotechnology holds immense potential in revolutionizing drug delivery systems for keratoplasty, enabling targeted and controlled release of therapeutic agents.[78]

Nanoparticles for drug delivery

Nanoparticles can be engineered to encapsulate drugs and deliver them directly to the target site, such as the cornea. These nanoparticles can protect the drugs from degradation, enhance their penetration into corneal tissues, and enable sustained release, reducing the need for frequent administrations. This approach can enhance the therapeutic efficacy of medications used in the postoperative management of keratoplasty patients.

Bioactive coatings

Nanotechnology can also be utilized to develop bioactive coatings for corneal grafts. These coatings can release bioactive molecules or growth factors that promote graft integration, inhibit inflammation, and prevent infection. By modulating the microenvironment at the graft–host interface, nanotechnology-based coatings can improve graft survival and long-term outcomes.[79]

ROBOTICS AND AUTOMATION IN SURGERY

Advancements in robotics and automation are poised to transform the field of keratoplasty, enhancing surgical precision, efficiency, and outcomes.

Robot-assisted corneal transplantation

Robotic systems can assist surgeons in performing precise and controlled corneal incisions, graft dissections, and suturing. These systems offer improved maneuverability and stability, reducing the risk of surgical errors and optimizing graft placement.[80] Robot-assisted surgery also allows for the integration of imaging technologies, such as AS-OCT, to enhance real-time visualization and feedback during the procedure.[81]

Artificial intelligence and machine learning

Machine learning algorithms can analyze large datasets of corneal images, patient data, and surgical outcomes to develop predictive models and personalized treatment plans.[82] By harnessing the power of artificial intelligence, surgeons can make more informed decisions regarding graft selection, surgical techniques, and postoperative management, leading to better patient outcomes.

In conclusion, the future of keratoplasty holds tremendous promise with advancements in artificial corneas, bioengineered constructs, gene therapy, nanotechnology-based drug delivery systems, and robotics. These emerging technologies have the potential to overcome the limitations of traditional techniques, improve graft survival rates, reduce complications, and enhance visual outcomes for patients with corneal diseases.[83] As research and innovation continue to progress, ophthalmologists can look forward to a new era in keratoplasty, where personalized treatments and state-of-the-art technologies converge to provide the best possible care for their patients.[84]

POTENTIAL BENEFITS AND CHALLENGES OF NEWER TECHNIQUES IN KERATOPLASTY

The newer techniques in keratoplasty offer several potential benefits over traditional approaches. They provide more targeted and selective transplantation, allowing for better preservation of healthy corneal tissue and faster visual rehabilitation. The use of advanced imaging modalities, such as AS-OCT, enhances preoperative evaluation, intraoperative guidance, and postoperative assessment. In addition, the development of artificial corneas, bioengineered constructs, gene therapy, nanotechnology-based drug delivery systems, and robotics holds the promise of overcoming limitations such as donor tissue shortage, graft rejection, and surgical complications.

However, these newer techniques also come with their own set of challenges. The learning curve associated with adopting these techniques may require additional training and expertise for surgeons. Cost considerations, availability of equipment, and long-term outcomes are important factors that need to be considered when implementing these techniques. Furthermore, continued research is necessary to optimize outcomes, reduce complications, and establish the long-term efficacy and safety of these newer approaches.

IMPLICATIONS FOR THE FUTURE OF KERATOPLASTY

The advancements in newer techniques discussed in this review article have significant implications for the future of keratoplasty. These techniques offer the potential for improved graft survival, enhanced visual outcomes, reduced postoperative complications, and increased patient satisfaction. Personalized treatment approaches, such as gene therapy and bioengineered constructs, may minimize the need for donor corneal tissue and reduce the risk of graft rejection. Nanotechnology-based drug delivery systems can provide targeted and sustained release of medications, optimizing therapeutic outcomes. The integration of robotics and automation can enhance surgical precision, efficiency, and patient safety.

AREAS FOR FURTHER RESEARCH AND ADVANCEMENT

Although substantial progress has been made in the field of keratoplasty, there are several areas that warrant further research and advancement. Long-term studies are needed to evaluate the durability and stability of newer techniques, ensuring their sustained efficacy over time. Comparative studies and randomized controlled trials are necessary to establish the superiority of these techniques over traditional approaches. Standardization of surgical protocols, postoperative management strategies, and outcome measures will facilitate meaningful comparisons and data interpretation.

In addition, research focusing on improving graft survival, minimizing complications, and optimizing visual outcomes is essential. Continued investigation into the development of artificial corneas, bioengineered constructs, gene therapy, nanotechnology-based drug delivery systems, and robotics will pave the way for innovative solutions in the field of keratoplasty. Furthermore, the integration of artificial intelligence and machine learning algorithms in analyzing large datasets holds the potential for personalized treatment planning and predictive models.

CONCLUSION

The newer techniques discussed in this review article have the potential to revolutionize the field of keratoplasty. They offer improved surgical outcomes, enhanced visual rehabilitation, and personalized treatment approaches. While challenges and areas for further research exist, the advancements in artificial corneas, bioengineered constructs, gene therapy, nanotechnology-based drug delivery systems, and robotics demonstrate a promising future for keratoplasty. Ongoing collaboration between clinicians, researchers, and industry stakeholders will be vital in translating these advancements into routine clinical practice, ultimately benefiting patients with corneal diseases worldwide.

Conflicts of interest

There are no conflicts of interest.

Funding Statement

Nil.