Whole-eye transplantation: Current challenges and future perspectives

Whole-eye transplantation emerges as a frontier in ophthalmology,promising a transformative approach to irreversible blindness.Despite advancements,formidable challenges persist.Preservation of donor eye viability post-enucleation necessitates meticulous surgical techniques to optimize retinal integrity and ganglion cell survival.Overcoming the inhibitory milieu of the central nervous system for successful optic nerve regeneration remains elusive,prompting the exploration of neurotrophic support and immunomodulatory interventions.Immunological tolerance,paramount for graft acceptance,confronts the distinc-tive immunogenicity of ocular tissues,driving research into targeted immunosup-pression strategies.Ethical and legal considerations underscore the necessity for stringent standards and ethical frameworks.Interdisciplinary collaboration and ongoing research endeavors are imperative to navigate these complexities.Biomaterials,stem cell therapies,and precision immunomodulation represent promising avenues in this pursuit.Ultimately,the aim of this review is to critically assess the current landscape of whole-eye transplantation,elucidating the challenges and advancements while delineating future directions for research and clinical practice.Through concerted efforts,whole-eye transplantation stands to revolu-tionize ophthalmic care,offering hope for restored vision and enhanced quality of life for those afflicted with blindness.

Two become one:combination of two risk factors in a new glaucoma animal model

Glaucoma is a group of eye diseases characterized by progressive loss of retinal ganglion cells(RGCs)and optic nerve degeneration.During this process,the visual field is reduced,and blindness may ultimately occur.Worldwide,glaucoma is the second leading cause of blindness,with about 80 million people affected.Glaucoma is a multifactorial disease and due to its complexity,the exact pathomechanisms are not fully understood yet.However,different risk factors,such as elevated intraocular pressure(IOP),age,or myopia,have been identified to date(EGS,2021).

Clinical associations of corneal neuromas with ocular surface diseases

Corneal neuromas,also termed microneuromas,refer to microscopic,irregula rly-shaped enlargements of terminal subbasal nerve endings at sites of nerve damage or injury.The formation of corneal neuromas results from damage to corneal nerves,such as following corneal pathology or corneal or intraocular surge ries.Initially,denervated areas of sensory nerve fibers become invaded by sprouts of intact sensory nerve fibers,and later injured axons regenerate and new sprouts called neuromas develop.In recent years,analysis of corneal nerve abnormalities including corneal neuromas which can be identified using in vivo confocal microscopy,a non-invasive imaging technique with microscopic resolution,has been used to evaluate corneal neuropathy and ocular surface dysfunction.Corneal neuromas have been shown to be associated with clinical symptoms of discomfort and dryness of eyes,and are a promising surrogate biomarker for ocular surface diseases,such as neuropathic corneal pain,dry eye disease,diabetic corneal neuropathy,neurotrophic keratopathy,Sjogren's syndrome,bullous keratopathy,post-refra ctive surgery,and others.In this review,we have summarized the current literature on the association between these ocular surface diseases and the presentation of corneal microneuromas,as well as elaborated on their pathogenesis,visualization via in vivo confocal microscopy,and utility in monitoring treatment efficacy.As current quantitative analysis on neuromas mainly relies on manual annotation and quantification,which is user-dependent and labor-intensive,future direction includes the development of artificial intelligence software to identify and quantify these potential imaging biomarkers in a more automated and sensitive manner,allowing it to be applied in clinical settings more efficiently.Combining imaging and molecular biomarkers may also help elucidate the associations between corneal neuromas and ocular surface diseases.

Does HSP27 injection induce glaucoma damage in mice?

In a further aging society,excellent eyesight is an integral part of overall well-being and quality of life.Preserving good vision is crucial to maintaining mobility,independence,and mental health.There can be several reasons for visual impairment in elderly people,these include age-related macular degeneration,the leading cause of vision loss among older adults,cataract,glaucoma,diabetic retinopathy,retinal detachment,and others.

Mixed-decomposed convolutional network:A lightweight yet efficient convolutional neural network for ocular disease recognition

Eye health has become a global health concern and attracted broad attention.Over the years,researchers have proposed many state-of-the-art convolutional neural networks(CNNs)to assist ophthalmologists in diagnosing ocular diseases efficiently and precisely.However,most existing methods were dedicated to constructing sophisticated CNNs,inevitably ignoring the trade-off between performance and model complexity.To alleviate this paradox,this paper proposes a lightweight yet efficient network architecture,mixeddecomposed convolutional network(MDNet),to recognise ocular diseases.In MDNet,we introduce a novel mixed-decomposed depthwise convolution method,which takes advantage of depthwise convolution and depthwise dilated convolution operations to capture low-resolution and high-resolution patterns by using fewer computations and fewer parameters.We conduct extensive experiments on the clinical anterior segment optical coherence tomography(AS-OCT),LAG,University of California San Diego,and CIFAR-100 datasets.The results show our MDNet achieves a better trade-off between the performance and model complexity than efficient CNNs including MobileNets and MixNets.Specifically,our MDNet outperforms MobileNets by 2.5%of accuracy by using 22%fewer parameters and 30%fewer computations on the AS-OCT dataset.

Optimal transcorneal electrical stimulation parameters for preserving photoreceptors in a mouse model of retinitis pigmentosa

Retinitis pigmentosa is a hereditary retinal disease that affects rod and cone photoreceptors,leading to progressive photoreceptor loss.Previous research supports the beneficial effect of electrical stimulation on photoreceptor survival.This study aims to identify the most effective electrical stimulation parameters and functional advantages of transcorneal electrical stimulation(tcES)in mice affected by inherited retinal degeneration.Additionally,the study seeked to analyze the electric field that reaches the retina in both eyes in mice and post-mortem humans.In this study,we recorded waveforms and voltages directed to the retina during transcorneal electrical stimulation in C57BL/6J mice using an intraocular needle probe with rectangular,sine,and ramp waveforms.To investigate the functional effects of electrical stimulation on photoreceptors,we used human retinal explant cultures and rhodopsin knockout(Rho^(-/-))mice,demonstrating progressive photoreceptor degeneration with age.Human retinal explants isolated from the donors’eyes were then subjected to electrical stimulation and cultured for 48 hours to simulate the neurodegenerative environment in vitro.Photoreceptor density was evaluated by rhodopsin immunolabeling.In vivo Rho^(-/-)mice were subjected to two 5-day series of daily transcorneal electrical stimulation using rectangular and ramp waveforms.Retinal function and visual perception of mice were evaluated by electroretinography and optomotor response(OMR),respectively.Immunolabeling was used to assess the morphological and biochemical changes of the photoreceptor and bipolar cells in mouse retinas.Oscilloscope recordings indicated effective delivery of rectangular,sine,and ramp waveforms to the retina by transcorneal electrical stimulation,of which the ramp waveform required the lowest voltage.Evaluation of the total conductive resistance of the post-mortem human compared to the mouse eyes indicated higher cornea-to-retina resistance in human eyes.The temperature recordings during and after electrical stimulation indicated no significant temperature change in vivo and only a subtle temperature increase in vitro(~0.5-1.5°C).Electrical stimulation increased photoreceptor survival in human retinal explant cultures,particularly at the ramp waveform.Transcorneal electrical stimulation(rectangular+ramp)waveforms significantly improved the survival and function of S and M-cones and enhanced visual acuity based on the optomotor response results.Histology and immunolabeling demonstrated increased photoreceptor survival,improved outer nuclear layer thickness,and increased bipolar cell sprouting in Rho^(-/-)mice.These results indicate that transcorneal electrical stimulation effectively delivers the electrical field to the retina,improves photoreceptor survival in both human and mouse retinas,and increases visual function in Rho^(-/-)mice.Combined rectangular and ramp waveform stimulation can promote photoreceptor survival in a minimally invasive fashion.

Unlocking the versatile potential:Adipose-derived mesenchymal stem cells in ocular surface reconstruction and oculoplastics

This review comprehensively explores the versatile potential of mesenchymal stem cells(MSCs)with a specific focus on adipose-derived MSCs.Ophthalmic and oculoplastic surgery,encompassing diverse procedures for ocular and periocular enhancement,demands advanced solutions for tissue restoration,functional and aesthetic refinement,and aging.Investigating immunomodulatory,regenerative,and healing capacities of MSCs,this review underscores the potential use of adipose-derived MSCs as a cost-effective alternative from bench to bedside,addressing common unmet needs in the field of reconstructive and regenerative surgery.

Effect of focal laser photocoagulation in eyes with mild to moderate non-proliferative diabetic retinopathy

AIM：To report the effect of focal laser photocoagulation on both the severity of hard exudates（HEs） and the rate of disease progression in eyes with mild to moderate non-proliferative diabetic retinopathy（NPDR）.METHODS： We retrospectively reviewed the medical records of 33 patients（60 eyes） who had been diagnosed with mild to moderate NPDR between January 2006 and December 2012.The patients were divided into 2 groups：Group A（38 eyes in 20 patients treated using focal laser photocoagulation） and Group B（treated without laser photocoagulation）.We also reviewed the best corrected visual acuity measurements,and the fundus photographs taken at both baseline and follow-up visits. RESULTS： In Group A,HE severity grade had decreased significantly from baseline to the final visit（P 〈0.05）,but this was not the case in Group B（P =0.662）.The cumulative probabilities of retinopathy progression at 5y were 26% in Group A and 30% in Group B.KaplanMeier survival curves showed no significant difference between the groups with regard to retinopathy progression（P =0.805）.CONCLUSION： Focal laser photocoagulation reduced the levels of HEs in eyes with mild to moderate NPDR.However,the treatment was not able to decelerate the progression of DR.

Changes of tear film lipid layer thickness by 3% diquafosol ophthalmic solutions in patients with dry eye syndrome

AIM: To evaluate the quantitatively changes in lipid layer thickness(LLT) when 3% diquafosol eye drop is used for dry eye patients using the tear film interferometer. METHODS: A total 124 participants(32 males, 92 females;mean age, 28.9 y) diagnosed with dry eye disease(DED) received topical instillation of 4 ophthalmic solutions in one eye: diquafosol, normal saline, 0.1% sodium hyaluronate and 0.3% gatifloxacin, in a masked manner. LLT was measured using an interferometer at baseline and 20 min after the instillation of each ophthalmic solutions.RESULTS: Changes of LLT after instillation(nm, mean± standard error) were as follows: 12.6±2.0 for diquafosol(P<0.001), 1.2±2.2 for normal saline(P=0.301), 1.5±2.0 for hyaluronate(P=0.495), and 0.5±3.2 for gatifloxacin(P=0.884).CONCLUSION: Topical instillation of diquafosol increases tear film LLT in DED patients. Diquafosol 3% eye drop might be effective treatment option of evaporative DED with meibomian gland dysfunction.

Bleb needling outcomes for failed trabeculectomy blebs in Asian eyes: a 2-year follow up

·AIM: To describe the outcomes of bleb needling in primary glaucoma in an Asian tertiary eye centre over a2 y period. To compare the success rates between primary angle-closure glaucoma(PACG) and primary open angle glaucoma(POAG). Lastly, to identify factors associated with success of bleb needling.·METHODS: This was a retrospective review of 227 patients who underwent bleb needling between June2009 and June 2011 in Singapore National Eye Centre.The 5-fluorouracil(5-FU) augmented bleb needling was performed either at the slit lamp or in the operating theatre. Repeat bleb needlings were performed as necessary. Complete success was defined as maintenance of intraocular pressure(IOP) ≥6 mm Hg and ≤21 mm Hg, in the absence of further surgery or use of antiglaucoma medication. Qualified success met the above criteria with or without use of antiglaucoma medications.· RESULTS: One hundred and seventy-five eyes completed the two-year follow up. Sixty-nine percent of participants had POAG and 31% had PACG. The mean interval between filtering surgery and bleb needling was299.9 ±616.4d for POAG and 167.1 ±272.2d for PACG.Mean needling attempts were 1.9±1.4 and 2±1.6 for POAG and PACG respectively. In general, there was a statistically significant reduction of IOP ranging from21.9% to 26.8% from month 1 through to month 24. The complete success rates at month 6 were 70.0% for POAG and 65.7% for PACG. At month 12, this decreased to62.2% for POAG and PACG and at month 24, 57.9% for POAG and 63.0% for PACG respectively. The qualified success rates at month 6 for POAG and PACG were23.8% and 29.9% respectively, 32.2% and 29.2% at month12, and 34.7% and 29.6% at month 24. The success ratesbetween POAG and PACG were not significantly different(P 】0.05 for complete and qualified success at months 6,12 and 24). An increased number of needlings and higher pre-needling IOP were associated with failure.·CONCLUSION: The 5-FU augmented bleb needling within one year of trabeculectomy in Asian eyes can provide clinically significant IOP lowering of more than20% for 2y. POAG and PACG had similar complete success rates(58% and 63% respectively). Factors associated with greater risk of procedure failure included increased number of needlings and higher pre-needling IOP. Asian eyes have a greater propensity for scarring but bleb needling, if performed in a timely manner can rescue bleb function.

Factors influencing subjective symptoms in dry eye disease

AIM: To retrospectively investigate the association between dry eye symptoms and clinical or in vivo confocal microscopy parameters in patients with dry eye disease(DED), and to compare these parameters between eyes with DED and normal subjects.METHODS: This retrospective, cross-sectional, controlled study comprised 25 consecutive patients with non-Sj?gren dry eye disease and age-and sex-matched 25 healthy subjects. Each patient underwent a complete examination of the ocular surface in the following order: tear osmolarity measurements, InflammaDry test, tear break-up time, corneal fluorescein staining, Schirmer I test, subjective symptoms questionnaire using the dry eye-related qualityof-life score(DEQS), and in vivo confocal microscopy analysis of the central cornea. Beck depression inventory(BDI) as depressive scale and history of medications and smoking were also evaluated. Stepwise multiple regression analysis was used to assess the factors affecting the DEQS.RESULTS: In univariate analysis, DEQS was associated with tear break-up time(ρ=-0.48, P=0.01), oral medications, such as hypotensive drug(ρ=0.56, P=0.004) and antidepressant(ρ=0.57, P=0.003), and BDI(ρ=0.61, P=0.001) in patients with DED. In multiple regression analysis, explanatory variables relevant to the DEQS were the anti-depressant medications(P=0.04, partial regression coefficient B=21.04) and BDI(P=0.02, B=0.76, adjusted R2=0.54) in these patients. CONCLUSION: Our study shows a significant association between depression and dry eye symptoms. It suggests that dry eye symptoms associate with higher depressive symptoms and its medications, although our patients were not followed longitudinally.

Prevalence and associations of non-retinopathy ocular conditions among older Australians with self-reported diabetes:The National Eye Health Survey

AIM:To determine the prevalence and associations of non-retinopathy ocular conditions among older Australian adults with diabetes.METHODS:Multistage random-cluster sampling was used to select 3098 non-indigenous Australians aged 50 y or older(46.4%male)and 1738 indigenous Australians aged 40 y or older(41.1%male)from all levels of geographic remoteness in Australia.Participants underwent a standardised questionnaire to ascertain diabetes history,and a clinical examination to identify eye disease.We determined the prevalence of uncorrected refractive error,visually significant cataract,cataract surgery,age-related macular degeneration,glaucoma,ocular hypertension,retinal vein occlusion and epiretinal membrane among those with and without self-reported diabetes.RESULTS:Participants with self-reported diabetes had a higher prevalence of cataract surgery than those without diabetes(28.8%vs 16.9%,OR 1.78,95%CI:1.35-2.34 among non-indigenous Australians,and 11.3%vs 5.2%,OR 1.62,95%CI:1.22-2.14 among indigenous Australians).Diabetic retinopathy(DR)increased the odds of cataract surgery among self-reported diabetic indigenous and nonindigenous Australians(OR 1.89,P=0.004 and OR 2.33,P<0.001 respectively).Having diabetes for≥20 y and having vision-threatening DR increased the odds of cataract surgery among indigenous Australians with diabetes(OR 3.73,P=0.001 and 7.58,P<0.001,respectively).CONCLUSION:Most non-retinopathy ocular conditions are not associated with self-reported diabetes.However,to account for Australia’s worsening diabetes epidemic,interventions to reduce the impact of diabetes-related blindness should include increased cataract surgery services.

In vitro eye embryogenesis from induced pluripotent stem cells for ocular surface disease treatment

In their letter to Nature,Hayashi et al.describe a new method for the generation of ocular surface epitheliumlike cells by incubating human induced pluripotent stem cells(iPS)into four defined concentric zones mimicking the developing eye,which the authors named as self-formed ectodermal autonomous multi-zone(SEAM)(1).

Apoptotic retinal ganglion cell loss is accompanied by complement and cytokine response in theβB1-CTGF primary open-angle glaucoma mouse model

Glaucoma is a multifactorial disease and occurs in many different species.In humans,glaucoma is accounted one of the leading causes for blindness worldwide.Due to glaucoma's complexity,it is still unclear what pathomechanisms may be involved in its development in humans as well as in other species,such as canines.Diagnosis of glaucoma can be delayed because patients often do not notice a visual field loss until approximately30%of retinal ganglion cells(RGCs)are lost(Kerrigan-Baumrind et al.,2000).Although the exact undergoing pathomechanisms of glaucoma disease are not fully understood yet,an increased intraocular pressure(IOP)is related to RGCdeath and is considered the main risk factor.

The pathology behind glaucoma:what we already know using omics technologies

The term glaucoma encompasses a spectrum of eye diseases pathologically characterized by an irreversible loss of retinal ganglion cells and their associated axons. Patients initially suffer from gaps in their visual field, the part of the visual range that can be perceived without eye movement. In the early stages of the disease, this damage can be compensated very well by eye movements. This, in turn, means that glaucoma is often not diagnosed until the disease is more advanced.

Cost-benefit and discriminant validity of a stepwise dementia case-finding approach in an Asian older adult community

Background Case-finding is a recommended approach for dementia early detection in the community.Aims To investigate the discriminant validity and cost-effectiveness of a stepwise dementia case-finding approach in a Singaporean older adult community.Methods The two-phase study was conducted in the community from 2009 to 2015 in Singapore.A total of 3780 participants(age≥60 years)completed phase I(a brief cognitive screening);918 completed phase II and were included in the final analysis.In phase I,all participants were administered the Abbreviated Mental Test(AMT)and the Progressive Forgetfulness Question(PFQ).Those who screened positive on either test were invited to phase II,whereby the Mini-Mental State Examination(MMSE),Montreal Cognitive Assessment(MoCA)and a formal neuropsychological battery were administered,followed by the research diagnosis of no cognitive impairment,cognitive impairment no dementia(CIND)-Mild(≤2 impaired cognitive domains),CIND-Moderate(>2 impaired domains)or dementia.Receiver operating characteristic curve analyses were conducted for the different cognitive instruments.All discriminant indices were calculated,including sensitivity,specificity,positive and negative predictive values(NPV)and accuracy.Cost-effectiveness analysis was conducted by estimating the amount of screening time needed and the number of older adults requiring re-evaluation in two case-finding scenarios,ie,with or without preselection by the PFQ.Results The stepwise case-finding approach(preselection by the PFQ,then MMSE or MoCA or AMT)showed an excellent NPV(>99%)and accuracy(>86%)for excluding dementia-free cases.Without preselection by the PFQ,screening time for the three cognitive tools were 317.5,317.5 and 254 hours,with 159,302 and 175 screen-positive older adults involved in further evaluation.By adopting the stepwise case-finding approach,total screening time were 156.5,156.5 and 126.2 hours,which decreased by 50.7%,50.7% and 50.3% as compared with those without preselection.Furthermore,after preselection,only 98,167 and 145 screen-positive older adults required further evaluation,corresponding to a reduction of 38.4%,44.7% and 17.1% in the numbers compared with those without preselection.Conclusions A stepwise approach for dementia case-finding should be implemented in the community to minimise the time and resources needed for large-scale early detection of dementia.

Neuroaxonal and cellular damage/protection by prostanoid receptor ligands,fatty acid derivatives and associated enzyme inhibitors

Cellular and mitochondrial membrane phospholipids provide the substrate for synthesis and release of prostaglandins in response to certain chemical,mechanical,noxious and other stimuli.Prostaglandin D_(2),prostaglandin E_(2),prostaglandin F_(2)α,prostaglandin I_(2)and thromboxane-A_(2)interact with five major receptors(and their sub-types)to elicit specific downstream cellular and tissue actions.In general,prostaglandins have been associated with pain,inflammation,and edema when they are present at high local concentrations and involved on a chronic basis.However,in acute settings,certain endogenous and exogenous prostaglandins have beneficial effects ranging from mediating muscle contraction/relaxation,providing cellular protection,regulating sleep,and enhancing blood flow,to lowering intraocular pressure to prevent the development of glaucoma,a blinding disease.Several classes of prostaglandins are implicated(or are considered beneficial)in certain central nervous system dysfunctions(e.g.,Alzheimer’s,Parkinson’s,and Huntington’s diseases;amyotrophic lateral sclerosis and multiple sclerosis;stroke,traumatic brain injuries and pain)and in ocular disorders(e.g.,ocular hypertension and glaucoma;allergy and inflammation;edematous retinal disorders).This review endeavors to address the physiological/pathological roles of prostaglandins in the central nervous system and ocular function in health and disease,and provides insights towards the therapeutic utility of some prostaglandin agonists and antagonists,polyunsaturated fatty acids,and cyclooxygenase inhibitors.

小鼠视神经再生研究动物模型的建立

目的 总结制作小鼠视神经完全截断性动物模型作为视神经再生研究的经验和体会。方法 将雄性Bcl-2高表达转基因小鼠（Bcl-2 transgenic mice）和受GFAP启动子控制表达疱疹病毒-胸苷激酶转基因雌性小鼠（GFAP-TK）交配产生的4只8～12周成年小鼠（20～30g），Bcl-2／GFAP-TK双转基因小鼠作为实验组，同周龄4只Bcl-2转基因小鼠作为对照组。其中Bcl-2／GFAP-TK双转基因小鼠皮下植入缓释泵，连续7d释放更昔洛韦（GCV）100mg·kg^-1·d“^-1选择性地去除视神经损伤后激活的星形胶质细胞。更昔洛韦缓释泵植入术后2d在两组动物中制作右侧单眼标准完全性视神经钳夹损伤模型，视神经钳夹10d后获取组织标本。采用免疫荧光染色特异性检测再生轴突纤维并进行定量分析；结合罗丹明的霍乱毒索B亚单位（CTB-R）或增强表达绿色荧光蛋白的复制缺陷型腺相关病毒（AAV-EGFP）用作顺行性标记物以显示再生轴突是否到达大脑靶器官。结果 在Bcl-2／GFAP-TK双转基因小鼠中存在免疫荧光阳性的再生视神经轴突，再生轴突计数为71．99±24．04，并可见生长锥（growth cone）样结构，但是再生轴突纤维未能延伸达到大脑靶器官。在对照组Bcl-2转基因小鼠中未见明显再生迹象。结论 小鼠视神经完全截断性动物模型可用于视神经病变的再生研究。

rhG-CSF促进体外培养神经干细胞的增殖

目的探讨重组人粒细胞集落刺激因子(rhG-CSF)对小鼠胚胎神经干细胞(NSCs)增殖的作用。方法分离培养小鼠NSCs,通过向培养基中添加G-CSF(10、30、60、100和200μg/L),四甲基偶氮唑蓝(MTT)比色法以及5-溴-2'-脱氧尿苷(BrdU)免疫荧光染色标记检测NSCs的增殖。免疫印迹法检测NSCs增殖时信号转导与转录激活因子3(STAT3)和磷酸化信号转导和转录激活因子3(p-STAT3)的表达。结果神经干细胞表达G-CSF受体,细胞活性随G-CSF的浓度不同表现出一定的剂量依赖性,当G-CSF的浓度为100μg/L时细胞的活性最高。G-CSF处理组的细胞增殖活性明显高于对照组。进一步证实,在G-CSF处理后,p-STAT3的表达则在5 min开始升高,30 min到达峰值,之后开始下降,至75 min接近正常水平。加入G-CSF受体的抗体后,p-STAT3的活化现象消失,并且细胞的增殖也明显低于G-CSF作用组,和对照组接近。结论 rhG-CSF可促进小鼠NSCs的增殖,其作用机制可能是通过细胞表面的G-CSF-R促进STAT3的活化。G-CSF可能作用于内源性NSCs的活化和增殖。

Fat or fillers:The dilemma in eyelid surgery

The aging of the periocular region has always aroused great interest.A fresh,young,and attractive sight determined an ever-greater attention to surgical and non-surgical techniques to obtain this result.In particular,the change in the concept of a young look,considered then“full”,led to the increasing use of surgical(fat grafting)or medical(hyaluronic acid)filling techniques.Eyelid rejuvenation became increasingly popular in the field of cosmetic treatments,with a focus on achieving a youthful and refreshed appearance.Among the various techniques available,the choice between using fat grafting or fillers presented a clinical dilemma.In particular,what surgery considered of fundamental importance was a long-lasting result over time.On the other hand,aesthetic medicine considered it fundamental not to have to resort to invasive treatments.But what was the reality?Was there one path better than the other,and above all,was there a better path for patients?The minireview aims to explore the physiopathology,diagnosis,treatment options,prognosis,and future studies regarding this dilemma.We analyzed the literature produced in the last 20 years comparing the two techniques.Current literature reveals advancements in biomaterials,stem cell research and tissue engineering held promise for further enhancing the field of eyelid rejuvenation.The choice between fat grafting and fillers in eyelid cosmetic treatments presented a clinical dilemma.Understanding physiopathology,accurately diagnosing eyelid aging,exploring treatment options,assessing prognosis,and conducting future studies were essential for providing optimal care to patients seeking eyelid rejuvenation.